Slide 1: Biogen Thematic Pipeline Seminar: Lupus
September 3, 2025 BIOGEN THEMATIC PIPELINE SEMINAR LUPUS
Slide 2: Forward-Looking Statements
FORWARD-LOOKING STATEMENTS 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
Slide 3: Call Participants
CALL PARTICIPANTS Priya Singhal, M.D., Daniel Quirk, M.D., Diana Gallagher, Adam Meyers, M.P.H. M.P.H., M.B.A. M.D. M.B.A., M.S. Head of Development Chief Medical Officer, Head Head of Clinical Development, Head of Immunology and of Medical Affairs MS&I and AD New Disease Areas Franchise 3
Slide 4: Agenda
AGENDA Opening Remarks Priya Singhal, M.D., M.P.H. Head of Development Lupus Overview Daniel Quirk, M.D., M.P.H., M.B.A. Chief Medical Officer, Head of Medical Affairs Late-stage Lupus Programs: Diana Gallagher, M.D. Dapirolizumab Pegol in SLE Head of Clinical Development, MS&I and AD Q+A All partic
Slide 5: Opening Remarks
OPENING REMARKS Priya Singhal, M.D., M.P.H. Head of Development
Slide 6: We Are on a Journey with the Aim of Building the New Biogen
WE ARE ON A JOURNEY WITH THE AIM OF BUILDING THE NEW BIOGEN Strategic Objectives Maximize the profitability of the legacy Continue to build momentum of ongoing Advance our high conviction late-stage MS business drug launches pipeline to support long-term growth Dapirolizumab Pegol* BIIB080^ * (SLE)
Slide 7: Pipeline Now Includes Multiple High Scientific Conviction Late-Stage Assets
PIPELINE NOW INCLUDES MULTIPLE HIGH SCIENTIFIC CONVICTION LATE-STAGE ASSETS Phase 1 Phase 2 Phase 3 Lecanemab (Aβ mAb)* – Preclinical AD Alzheimer’s disease BIIB080 (tau ASO)^ – Early AD Dapirolizumab pegol (anti-CD40L)* – SLE Litifilimab (anti-BDCA2 mAb) – SLE Immunology Litifilimab (anti-BDCA2 mAb
Slide 8: Our Immunology Portfolio Is Anchored by Two Phase 3 Lupus Assets
OUR IMMUNOLOGY PORTFOLIO IS ANCHORED BY TWO PHASE 3 LUPUS ASSETS Phase 3 • Third ever agent to successfully deliver positive Phase 3 data in SLE Dapirolizumab pegol SLE • Confirmatory trial results expected Dapirolizumab-pegol SLE Phase 3 in 2027-2028 Phase 3 • Potential first-in-class once-monthly
Slide 9: Opportunity to Deliver Meaningful New Medicines for Patients with Lupus
OPPORTUNITY TO DELIVER MEANINGFUL NEW MEDICINES FOR PATIENTS WITH LUPUS We believe lupus is a highly underserved market with significant potential for market expansion Lupus is estimated to affect millions of patients globally* Low treatment rates due to heterogeneity and lack of treatment options D
Slide 10: We Believe Our Proven Track Record in MS Positions Us to Succeed in Lupus
WE BELIEVE OUR PROVEN TRACK RECORD IN MS POSITIONS US TO SUCCEED IN LUPUS Characteristics of MS also ~30 years in neuro-immunology pioneering associated with Lupus1 the development of MS treatments • Heterogeneous disease and symptoms • Younger, predominantly female • Associated with flares, remissi
Slide 11: We Have an Opportunity to Deliver Exciting New Medicines for Patients with Lupus
WE HAVE AN OPPORTUNITY TO DELIVER EXCITING NEW MEDICINES FOR PATIENTS WITH LUPUS We have two Phase 3 assets that have demonstrated strong clinical data in lupus Lupus has the potential to grow into a larger multi-billion dollar market with new approved treatment options We believe our proven track r
Slide 12: Lupus Overview
LUPUS OVERVIEW Daniel Quirk, M.D., M.P.H., M.B.A. Chief Medical Officer, Head of Medical Affairs
Slide 13: Lupus Is a Very Complex, Heterogeneous Set of Diseases
LUPUS IS A VERY COMPLEX, HETEROGENEOUS SET OF DISEASES Complex biology Multiple organs impacted Variability in patient experience CNS • Involves both the adaptive LUNG • Symptoms vary by patient and innate immune systems HEART • Response to therapy is highly • Tissue damage caused by KIDNEY variable
Slide 14: Lupus Is Composed of Distinct Diseases with SLE and CLE Most Common
LUPUS IS COMPOSED OF DISTINCT DISEASES WITH SLE AND CLE BEING THE MOST COMMON SLE CLE U.S. ~75k ~40k EU4+UK Japan ~95k ~235k ~190k ~280k • Relapsing-remitting disease course with flares that can • Skin-based form of lupus with symptoms including rash, cause severe organ damage pain, hair loss, itch
Slide 15: SLE
SLE SYSTEMIC LUPUS ERYTHEMATOSUS
Slide 16: SLE Is a Chronic Systemic Autoimmune Disease with Broad Clinical Manifestations
SLE IS A CHRONIC SYSTEMIC AUTOIMMUNE DISEASE WITH A BROAD RANGE OF CLINICAL MANIFESTATIONS Typical symptoms Patient Population • Joint involvement observed in >90% of patients1 • ~235k patients in the U.S.* • Skin manifestations in up to 85% of patients7 • Disproportionately affects younger women (1
Slide 17: SLE Is Characterized by Phases of Flares Followed by Low Disease Activity or Remission
SLE IS CHARACTERIZED BY PHASES OF FLARES FOLLOWED BY LOW DISEASE ACTIVITY OR REMISSION • SLE disease activity commonly SLE disease activity and fluctuates • ~25% of patients flare within inflammation 1–2 years after achievement Damage accrual of low disease activity or remission1 • Increased organ d
Slide 18: A Conversation with Dr. Karen Costenbader, MD, MPH
A CONVERSATION WITH DR. KAREN COSTENBADER, MD, MPH 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,
Slide 19: Significant Opportunity to Expand Treatment and Benefit More Patients with SLE
SIGNIFICANT OPPORTUNITY TO EXPAND TREATMENT AND BENEFIT MORE PATIENTS WITH SLE 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 activ
Slide 20: CLE
CLE CUTANEOUS LUPUS ERYTHEMATOSUS
Slide 21: CLE Primarily Manifests in the Skin and Mucosal Tissues
CLE PRIMARILY MANIFESTS IN THE SKIN AND MUCOSAL TISSUES, WHICH CAN OCCUR WITH OR WITHOUT SYSTEMIC MANIFESTATIONS Typical symptoms Patient Population • Photosensitivity • Itch • ~280k patients in the U.S.* • Disproportionately women1 • Hair loss • Scarring • People who are Black or Hispanic have a hi
Slide 22: CLE Is Distinct Disease Associated with Skin Manifestations
CLE IS DISTINCT DISEASE ASSOCIATED WITH SKIN MANIFESTATIONS Chronic Skin Manifestations Photosensitivity2 Hair loss3 Pain2 Rash1 Itch2 Disfiguring scars1,2,4 Dyspigmentation1,2 Image 1: erythema; image 2: erythema, scale, infiltration; image 3: alopecia; image 4: erythema, scale, edema; CLE = cutane
Slide 23: A Conversation with Dr. Joseph Merola, MD
A CONVERSATION WITH DR. JOSEPH MEROLA, MD, MMSc, FAAD, FACR Joseph F. Merola, M.D. MMSc, FAAD FACR Dermatologist, Rheumatologist Medical and Scientific Board, Lupus Foundation President Elect, Rheumatology – Dermatology Society 23
Slide 24: Clear Opportunity to Improve Treatment Options for CLE Patients
THERE IS A CLEAR OPPORTUNITY TO IMPROVE TREATMENT OPTIONS FOR CLE PATIENTS 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 s
Slide 25: Our Late-Stage SLE Programs
OUR LATE-STAGE SLE PROGRAMS Diana Gallagher Head of Clinical Development, MS&I and AD
Slide 26: Biology of Lupus Involves Several Reinforcing Pathways
BIOLOGY OF LUPUS INVOLVES SEVERAL REINFORCING PATHWAYS THAT PROVIDE DISTINCT OPPORTUNITIES FOR INTERVENTION Key pDCs (plasmacytoid Dendritic Cells) T-cells cause direct tissue B-cells generate autoantibodies Immune produce excess IFN-I and other damage and secrete that cause inflammation and cytokin
Slide 27: Our Pipeline Spans Multiple Points of Intervention in the Lupus Cascade
OUR PIPELINE SPANS MULTIPLE POINTS OF INTERVENTION IN THE LUPUS CASCADE BDCA2 DCs, Type 1 Macrophages, IFNs T cell B-cell B cell and pDC Monocytes CD38 CD32a (FcγRIIa) Autoantibodies and Immune complexes Proinflammatory mediators Innate Immune System (e.g., IFNs and cytokines) Adaptive Immune System
Slide 28: Dapirolizumab Pegol in SLE
DAPIROLIZUMAB PEGOL IN SLE FC-FREE PEGYLATED ANTIGEN-BINDING FRAGMENT
Slide 29: CD40L Is a Key Target to Disrupt CD40 Signaling
CD40L IS A KEY TARGET TO DISRUPT CD40 SIGNALING AND INTERRUPT THE IMMUNOLOGIC CASCADE IN SLE DCs, Type 1 Macrophages, B cell and T cell IFNs pDC Monocytes Proinflammatory mediators (e.g., IFNs and cytokines) Innate Immune System Adaptive Immune System • When CD40 binds to CD40L it signals the cell t
Slide 30: Dapirolizumab Pegol Designed to Deliver Efficacy Without Thrombosis Potential
DAPIROLIZUMAB PEGOL IS DESIGNED TO DELIVER EFFICACY WITHOUT THE POTENTIAL FOR THROMBOSIS SEEN WITH OLDER CD40L AGENTS Dapirolizumab pegol (DZP) Fab’ fragment • DZP is a pegylated antibody fragment designed to bind to CD40L • Lack of functional Fc domain abrogates the potential risk of Fc-mediated pl
Slide 31: Phase 3 Study Evaluating Safety and Efficacy in Patients with SLE
A PHASE 3 STUDY WAS CONDUCTED TO EVALUATE THE SAFETY AND EFFICACY IN PATIENTS WITH SLE Primary objective1 Key secondary objectives1 BICLA response rate at Week 48 • Achievement of BICLA response at Weeks 12 & 24 • Severe BILAG flares through Week 48 • Achievement of SRI-4 response at Week 48 • LLDAS
Slide 32: Dapirolizumab Pegol Only 3rd Agent to Meet Primary Endpoint in Global Phase 3 in SLE
DAPIROLIZUMAB PEGOL IS ONLY THE 3RD AGENT TO MEET THE PRIMARY ENDPOINT IN A GLOBAL PHASE 3 STUDY Dapirolizumab significantly improved disease activity in moderate to severe SLE 70 100 Primary endpoint First DZP+SOC (n=208) secondary endpoint Patients achieving BICLA response (%) 60 PBO+SOC (n=107) *
Slide 33: DZP Patients Achieved Meaningful Improvement in Steroid Use and Flares
DZP PATIENTS ACHIEVED A MEANINGFUL IMPROVEMENT IN STEROID USE AND REDUCTION IN FLARES 17% more patients on the DZP+SOC were able to 50.4% reduction in proportion of patients receiving reduce their steroids compared to PBO+SOC DZP+SOC with severe BILAG flares relative to patients receiving PBO+SOC DZ
Slide 34: Data Highlights Potential to Alleviate Fatigue and Improve Quality of Life
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 an
Slide 35: Dapirolizumab Pegol Was Generally Well Tolerated in the Phase 3 Study
DAPIROLIZUMAB PEGOL WAS GENERALLY WELL TOLERATED IN THE PHASE 3 STUDY DZP+SOC PBO+SOC n, (%) n=213 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 th
Slide 36: Preclinical Findings in Pregnancy Support a Potentially Differentiated Profile
PRECLINICAL FINDINGS IN PREGNANCY SUPPORT A POTENTIALLY DIFFERENTIATED PROFILE Based on current findings, DZP is not anticipated to cross the placenta to significant levels and supports further investigation in pregnant women In primates: • DZP caused no adverse outcomes on pregnancy or infant devel
Slide 37: Second Confirmatory PHOENYCS FLY Phase 3 Study Ongoing
SECOND CONFIRMATORY PHOENYCS FLY PHASE 3 STUDY ONGOING Double-blind Placebo (SoC only) (n=150)a period DZP 24 mg/kg + SoC q4w (n=300)a Screening Week: –2 0 4 8 12 16 20 24 28 32 36 40 44 48 54 Primary Safety IV infusion: endpoint follow-upb GC taperc Primary objective Key objectives Moderate-to-seve
Slide 38: Dapirolizumab Pegol Potential for Meaningfully Positive Impact on Patients
DAPIROLIZUMAB PEGOL HAS THE POTENTIAL TO HAVE A MEANINGFULLY POSITIVE IMPACT ON PATIENTS DZP is only the 3rd agent to show a positive global Phase 3 study in SLE Data show a 50% reduction in flares, meaningful reduction in corticosteroid use, as well as a quality-of-life improvement, including fatig
Slide 39: Question & Answers
QUESTION & ANSWERS
Slide 40: Litifilimab in SLE
LITIFILIMAB IN SLE BDCA2 INHIBITOR
Slide 41: Anti-BDCA2 Is a Potentially Attractive Approach for Reducing IFN-I Production
ANTI-BDCA2 IS A POTENTIALLY ATTRACTIVE APPROACH FOR REDUCING PRODUCTION OF IFN-I, CYTOKINES AND CHEMOKINES IN LUPUS • Production of IFN-I in pDC cells is BDCA2 inhibited by internalization of BDCA2 into the cell • This makes BDCA2 an attractive target to inhibit the production of IFN-I and other cyt
Slide 42: Litifilimab Is Designed to Bind BDCA2, Inhibiting IFN-I Production
LITIFILIMAB IS DESIGNED TO BIND TO BDCA2 THEREBY INHIBITING THE PRODUCTION OF IFN-I • 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
Slide 43: LILAC Was a Two-Part, Phase 2, Randomized, Double-Blind Study of Litifilimab
LILAC WAS A TWO-PART, PHASE 2, RANDOMIZED, DOUBLE-BLIND STUDY OF LITIFILIMAB Part A study design in participants with SLE and active skin disease and joint involvement1 28-DAY SCREENING Double-blind, placebo-controlled treatment period SELECT PERIOD ENDPOINTS Follow up 12 weeks • ANA and/or anti-dsD
Slide 44: Part A of the Phase 2 LILAC Study Met Its Primary Endpoint
PART A OF THE PHASE 2 LILAC STUDY MET ITS PRIMARY ENDPOINT Improved Joint Activity: Litifilimab significantly reduced the mean total number of active joints vs placebo Total active joint count*† in patients with SLE and active skin disease and joint involvement (N=132‡) (primary endpoint at Week 24)
Slide 45: Secondary Endpoints in LILAC Show Important Response in Skin and Overall Symptoms
SECONDARY ENDPOINTS IN LILAC ALSO SHOW IMPORTANT RESPONSE IN SKIN AND OVERALL SYMPTOMS CLASI-50 responses* (secondary endpoint at Week 24) 1 LSM difference (95% CI) 100 20.0% (−1.3, 41.3)1,2 90 Placebo + SoC (n=38) 60 50 Litifilimab 450 mg SC + SoC (n=39) Saw a meaningful improvement in skin manifes
Slide 46: Litifilimab Had Acceptable Safety Profile in LILAC Part A
LITIFILIMAB HAD AN ACCEPTABLE SAFETY PROFILE WITH NO INCREASED RISK OF INFECTION IN LILAC PART A Phase 2 LILAC Part A1,2 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 e
Slide 47: Two Phase 3 Studies Ongoing in SLE with First Data Expected in 2026
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
Slide 48: Litifilimab in CLE
LITIFILIMAB IN CLE BDCA2 INHIBITOR
Slide 49: Biopsies Show Plasmacytoid Dendritic Cells Accumulate in Skin Lesions
BIOPSIES SHOW PLASMACYTOID DENDRITIC CELLS ACCUMULATE IN SKIN LESIONS HIGHLIGHTING THE POTENTIAL FOR BDCA2 IN TREATING CLE pDC infiltration (measured by CD123 expression) • In CLE, pDCs migrate to the skin1 and frequently comprise 20–30% of dermal infiltrates2-4 • Therefore, anti-BDCA2 has the poten
Slide 50: LILAC Part B Phase 2 Study Design in CLE
LILAC WAS A TWO-PART, PHASE 2, RANDOMIZED, DOUBLE-BLIND STUDY OF LITIFILIMAB Part B study design in participants with CLE, with or without systemic manifestations1 28-DAY SCREENING Double-blind, placebo-controlled treatment period SELECT PERIOD ENDPOINTS 12-week follow-up period • Histologically con
Slide 51: Part B of the Phase 2 LILAC Study Met Its Primary Endpoint in CLE
PART B OF THE PHASE 2 LILAC STUDY MET ITS PRIMARY ENDPOINT IN CLE PATIENTS WITH OR WITHOUT SYSTEMIC MANIFESTATIONS Litifilimab significantly reduced skin disease activity vs placebo, on top of standard of care Percentage change in CLASI-A score from baseline over time (primary endpoint at Week 16)*
Slide 52: Litifilimab Also Showed Significant Depth of Response in CLE
LITIFILIMAB ALSO SHOWED SIGNIFICANT DEPTH OF RESPONSE IN CLE 100 LSM difference (95% CI) 60 CLASI-50 responses (secondary endpoint) 23.3% (2.9, 43.6)1 Participants responding (%) 48.0 46.5 44.0 40 37.5 38.5 37.5 38.5 32.0 Placebo (n=33) 28.0 26.9 Litifilimab 50 mg (n=26) 22.9 21.9 19.2 Litifilimab 1
Slide 53: Patient Exhibited Reduced Erythema, Scales, and Swelling on the Face
PATIENT EXHIBITED REDUCED ERYTHEMA, SCALES, AND SWELLING ON THE FACE After 24 weeks of litifilimab SC Q4W treatment: Patient with SLE and DLE exhibited reduced erythema, scales, and swelling on the face Images obtained with consent from the patient DLE = discoid lupus erythematosus; Q4W = every 4 we
Slide 54: AMETHYST Is Intended as a Registrational Study in CLE
AMETHYST IS INTENDED AS A REGISTRATIONAL STUDY TO EVALUATE LITIFILIMAB IN CLE AMETHYST study design1,2 KEY INCLUSION Double-blind, SELECT Extended placebo-controlled CRITERIA treatment period ENDPOINTS treatment period • Age ≥18 years Key secondary efficacy • Histologically confirmed CLE Litifilimab
Slide 55: LILAC Studies Support Compelling Proof of Concept in SLE and CLE
THE LILAC STUDIES SUPPORT COMPELLING PROOF OF CONCEPT FOR LITIFILIMAB IN BOTH SLE AND CLE SLE (Lilac A) CLE (Lilac B) Published September 7, 2022 N Engl J Med 2022;387:894-904 DOI: Published July 27, 2022 N Engl J Med 2022;387:321-331 DOI: 10.1056/NEJMoa2118025 10.1056/NEJMoa2118024 Further supporte
Slide 56: Litifilimab Has the Potential to Treat Patients in Both SLE and CLE
LITIFILIMAB HAS THE POTENTIAL TO TREAT PATIENTS IN BOTH SLE AND CLE 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
Slide 57: Concluding Remarks
CONCLUDING REMARKS Priya Singhal, M.D., M.P.H. Head of Development
Slide 58: Lupus Is a Key Component of a Strengthening Pipeline
LUPUS IS A KEY COMPONENT OF A STRENGTHENING PIPELINE TO SUPPORT OUR LONG-TERM GROWTH OBJECTIVE Regulatory Review in Phase 1 Phase 2 Phase 3 Certain Markets Lecanemab (Aβ mAb)* SC-AI BIIB142 (IRAK4 degrader)* – Lecanemab (Aβ mAb)* BIIB080 (tau ASO)^ Felzartamab Maintenance Autoimmune disease SC-AI In
Slide 59: Key Expected Milestones Over the Next 18 Months
OUR DISCIPLINED SCIENTIFIC APPROACH IS POISED TO DELIVER KEY EXPECTED MILESTONES OVER THE NEXT 18 MONTHS 3 Study Starts 4 Clinical Trial Readouts 2 Regulatory Decisions • Felzartamab Phase 3 in IgAN • Salanersen Phase 1b interim in • Zuranolone in PPD SMA Now approved in U.K. & • Felzartamab Phase 3
Slide 60: Question & Answers
QUESTION & ANSWERS