dapirolizumab pegol (CDP7657) / Biogen, UCB, Nektar Therap - LARVOL DELTA

Dapirolizumab pegol: Data readout from P3 PHOENYCS FLY trial (NCT06617325) for moderately-to-severe SLE between 2028 and 2030 (Biogen) - Q3 2025 Results

P3 data • Lupus • Systemic Lupus Erythematosus

Dapirolizumab Pegol, a Novel CD40L Inhibitor, Showed No Adverse Outcomes in an In Vivo Non-Human Primate Reprotoxicity Study and Displayed Minimal to No Human Placental Transfer in an Ex Vivo Study (ACR Convergence 2025) - P3 | "DZP showed no adverse outcomes on pregnancy or infant development post-birth in NHPs. In the ex vivo human placental model, DZP transfer was below the level of detection. These data align with lack of active placental transfer via the neonatal Fc receptor, causing minimal to no DZP transfer from mother to fetus, and suggest DZP may not be anticipated to cross the placenta to significant levels."

Adverse events • Preclinical • Inflammatory Arthritis • CD40LG

Alternative Definitions of Moderate Flares That Simulate Clinical Practice in Systemic Lupus Erythematosus: Post Hoc Exploration of Moderate Flares in Patients Treated with Dapirolizumab Pegol in a 48-week Phase 3 Trial (ACR Convergence 2025) - P3 | "Pts treated with DZP+SOC had fewer BILAG 2004 moderate flares, by all definitions considered, vs those treated with PBO+SOC. When allowing for longer time intervals over consecutive visits to evaluate moderate flares with the alternative definitions, greater rates of BILAG 2004 moderate flares were observed, particularly for pts receiving PBO+SOC, and greater differentiation between DZP+SOC and PBO+SOC was also observed. These results confirm a need to re-evaluate how flares are captured in SLE clinical trials; the alternative definitions of flares explored may better simulate clinical practice than the native definition of BILAG 2004 moderate flares."

Clinical • P3 data • Retrospective data • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG

Dapirolizumab Pegol Demonstrated Improvement in Quality of Life of Patients with Systemic Lupus Erythematosus: LupusQoL Results from a Phase 3 Trial (ACR Convergence 2025) - P3 | "Improvements in HRQoL were greater in patients treated with DZP+SOC compared with PBO+SOC across all LupusQoL domains, starting at the earliest time point (Wk 12) for some domains. These data, along with the previously reported significant improvements in overall disease activity,5 support the potential of DZP as a valuable treatment option in SLE to improve HRQoL."

Clinical • HEOR • P3 data • Fatigue • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG

Improvement of Fatigue, Musculoskeletal Pain, and Morning Stiffness in Patients with Systemic Lupus Erythematosus Treated with Dapirolizumab Pegol: 48-Week Results from a Phase 3 Trial (ACR Convergence 2025) - P3 | "Improvements in fatigue, musculoskeletal pain, and morning stiffness were greater in pts treated with DZP+SOC vs PBO+SOC. Alongside the previously reported improvements in clinical measures of SLE disease activity,3 these data suggest that DZP improves core pt-reported symptoms in SLE."

Clinical • P3 data • Fatigue • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Musculoskeletal Diseases • Musculoskeletal Pain • Pain • Rheumatology • Systemic Lupus Erythematosus • CD40LG

Achievement of Low Disease Activity and Remission in Patients with Systemic Lupus Erythematosus Treated with Dapirolizumab Pegol: 48-week Results from a Phase 3 Trial (ACR Convergence 2025) - P3 | "Treatment with DZP+SOC resulted in higher rates of achievement and time in the prognostically important endpoints of LLDAS and DORIS vs PBO+SOC. These findings provide further insights into the potential benefits of treatment with DZP for pts with SLE."

Clinical • P3 data • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG

Biogen to Present Additional Results from Phase 3 Study of Dapirolizumab Pegol in Systemic Lupus Erythematosus at ACR Convergence 2025 (GlobeNewswire) - "The presentations will show efficacy results of DZP across multiple endpoints including low disease activity/remission, flares, fatigue, joint pain and quality of life. Additional preclinical data will also be presented, demonstrating minimal to no placental transfer of DZP supporting further study in women before, during and after pregnancy....The additional data presented from the PHOENYCS GO trial at ACR suggest a broad impact across endpoints in this Phase 3 study. In the Phase 3 study, DZP met the primary endpoint of improvement of moderate-to-severe disease activity as assessed by achievement of BICLA after 48 weeks. As the first key secondary endpoint had a p-value = 0.1776, all subsequent secondary and tertiary endpoints are descriptive and nominal p-values are included."

P3 data • Preclinical • Systemic Lupus Erythematosus

Biogen Highlights Multiple Assets and Indications in Lupus (Biogen Press Release) - "The webcast will illustrate the science behind the portfolio and strategic opportunities to improve and expand treatment options for people with lupus. Specifically, it will feature the distinct mechanisms of action and compelling data supporting litifilimab and DZP, along with details of the Phase 3 designs and expected timing of data readouts."

Clinical • Systemic Lupus Erythematosus

PHOENYCS FLY: A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Sep 2027 ➔ May 2028 | Trial primary completion date: Sep 2027 ➔ May 2028

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Study to Evaluate the Safety and Tolerability of Dapirolizumab Pegol in Study Participants With Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=760 | Enrolling by invitation | Sponsor: UCB Biopharma SRL | Trial completion date: Apr 2029 ➔ Aug 2030 | Trial primary completion date: Apr 2029 ➔ Aug 2030

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

IMPROVEMENT OF FATIGUE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS TREATED WITH DAPIROLIZUMAB PEGOL: 48-WEEK RESULTS FROM A PHASE 3 TRIAL (EULAR 2025) - P3 | "Improvements in FACIT-Fatigue and all FATIGUE-PRO scales were greater in patients treated with DZP+SOC versus PBO+SOC. Alongside the previously reported significant improvements in overall SLE disease activity, [6] these data support the potential of DZP as a valuable treatment option for improving fatigue in SLE."

Clinical • P3 data • Fatigue • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG

INHIBITORY EFFECTS OF DAPIROLIZUMAB PEGOL, A MONOVALENT ANTI-CD40L PEG-CONJUGATED ANTIGEN-BINDING FRAGMENT LACKING AN FC DOMAIN, ON IN VITRO T FOLLICULAR HELPER/B CELL INTERACTIONS AND CYTOKINE PRODUCTION IN SYSTEMIC LUPUS ERYTHEMATOSUS (EULAR 2025) - P2, P3 | "DZP was shown to inhibit key T cell, B cell, and APC cell functions that drive SLE pathogenesis, leading to suppression of cytokines, and total and antigen-specific IgG production in vitro . These data support clinical and transcriptomic/proteomic findings from patients with SLE treated with DZP, where reductions of immunoglobulins and key pro-inflammatory cytokines have been observed [3, 4, 6, 7]. Overall, the data indicate that DZP modulates multiple pathways relevant to the pathogenesis of SLE."

IO biomarker • Preclinical • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG • CD8 • IFNG • IL10 • IL6

ACHIEVEMENT OF LOW DISEASE ACTIVITY AND REMISSION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS TREATED WITH DAPIROLIZUMAB PEGOL: 48-WEEK RESULTS FROM A PHASE 3 TRIAL (EULAR 2025) - P3 | "Compared with PBO+SOC, treatment with DZP+SOC resulted in higher rates of achievement and time in the prognostically important endpoints of LLDAS and DORIS. These findings provide further insights into the potential benefits of treatment with DZP for patients with SLE."

Clinical • P3 data • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG

DAPIROLIZUMAB PEGOL DEMONSTRATED SIGNIFICANT IMPROVEMENT IN SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE ACTIVITY: EFFICACY AND SAFETY RESULTS OF A PHASE 3 TRIAL (EULAR 2025) - P3 | "Other endpoints included the proportion of patients who achieved glucocorticoid tapering from >7.5 mg/day prednisone equivalent at baseline to ≤7.5 mg/day at Week 48, per EULAR 2019 treatment guidelines [3]. Treatment with DZP, a novel CD40L inhibitor, was associated with improvement in disease activity and glucocorticoid tapering in patients with SLE. DZP was generally well tolerated."

Clinical • P3 data • Cardiovascular • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Myocardial Infarction • Septic Shock • Systemic Lupus Erythematosus • CD40LG

Dapirolizumab Pegol Phase 3 Data in SLE Presented at the Annual European Congress of Rheumatology (EULAR) Show Improvement in Fatigue and Reduction in Disease Activity (Yahoo Finance) - P3 | N=321 | PHOENYCS GO (NCT04294667) | Sponsor: UCB Biopharma SRL | "UCB (Euronext Brussels: UCB) and Biogen Inc...presented additional detailed results from the Phase 3 PHOENYCS GO study evaluating dapirolizumab pegol (DZP), a novel Fc-free anti-CD40L drug candidate....Improvements in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores were greater in the DZP group (change from baseline, 8.9), compared with SOC alone (5.2; nominal p=0.0024) at Week 48. Using FATIGUE-PRO, a measure recently developed to capture the patient experience of fatigue in SLE, greater improvements from baseline (nominal p<0.05) were observed in people receiving DZP compared with SOC alone in the Physical Fatigue (change from baseline difference between groups,7.6), Mental and Cognitive (5.6), and Susceptibility to Fatigue (7.8) scales at Week 48."

P3 data • Systemic Lupus Erythematosus

Dapirolizumab pegol: Data readout from P3 PHOENYCS FLY trial (NCT06617325) for moderately-to-severe SLE in 2028 (Biogen) - Q4 & FY2024 Results

P3 data • Lupus • Systemic Lupus Erythematosus

PHOENYCS FLY: A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Mar 2027 ➔ Sep 2027 | Trial primary completion date: Mar 2027 ➔ Sep 2027

Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

On Growth Path for a Decade plus: Strong Launch Execution driving Company Growth (PRNewswire) - "Recruitment for the phase 3 study with Fenfluramine (5-HT agonist) in the treatment of CDKL5 deficiency disorder (CDD) has required more time than anticipated...The study is now fully recruited, and first headline results are expected in H1 2025...In December 2024, UCB and Biogen initiated the second Phase 3 trial of dapirolizumab pegol, PHOENYCS FLY, with first headline results expected in 2028...BE BOLD is the first head-to-head study in PsA evaluating the superiority of an IL-17A and IL-17F inhibitor to an IL-23 inhibitor. First headline results are expected in H2 2026."

P3 data • Genetic Disorders • Psoriatic Arthritis • Rare Diseases • Systemic Lupus Erythematosus

PHOENYCS FLY: A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: UCB Biopharma SRL | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

The True Value of Living Systematic Reviews (LSRs): A Case Report Within Systemic Lupus Erythematosus (SLE) (ISPOR-EU 2024) - "Belimumab, anifrolumab, dapirolizumab pegol, and deucravacitinib showed promising results in RCTs. An SLR search update 16 months after the primary search generated 18 new publications, providing a significant addition to the available evidence on current therapy options. The update provides insight into the appropriate cadence for LSRs and highlights efficiencies gained with LiveSLRTM."

Case report • Clinical • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Dapirolizumab Pegol Demonstrated Significant Improvement in Systemic Lupus Erythematosus Disease Activity: Efficacy and Safety Results of a Phase 3 Trial (ACR Convergence 2024) - P3 | "Per protocol, pts with a corticosteroid dose >7.5 mg/day prednisone equivalent were required to start tapering no later than Wk 8 to reach ≤7.5 mg/day. Treatment with DZP, a novel CD40L inhibitor, resulted in improvement in disease activity and corticosteroid tapering in pts with SLE; significantly more pts who received DZP+SOC achieved BICLA response vs PBO+SOC. DZP was generally well tolerated."

Clinical • Late-breaking abstract • P3 data • Cardiovascular • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Myocardial Infarction • Septic Shock • Systemic Lupus Erythematosus • CD40LG

Inhibitory Effects of Dapirolizumab Pegol, a Monovalent Anti-CD40L PEG-Conjugated Antigen-Binding Fragment Lacking a Functional Fc Domain, on In Vitro T Follicular Helper/B Cell Interactions and Cytokine Production in Systemic Lupus Erythematosus (ACR Convergence 2024) - P3 | "DZP was shown to inhibit key germinal center-relevant cell interactions leading to suppression of cytokine and total and antigen-specific IgG production in vitro. These data support clinical and transcriptomic/proteomic findings from patients with SLE treated with DZP, where reductions of immunoglobulins and key pro-inflammatory cytokines have been observed.4–6"

Preclinical • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD40LG • CD8 • IFNG • IL1B • IL6

Dapirolizumab Pegol Impacts Important Immunologic Pathways in Systemic Lupus Erythematosus: Pharmacodynamic Analysis of T Cell and Antigen Presenting Cell Pathways from a Phase 2b Trial (ACR Convergence 2024) - P2, P3 | "Beyond its known effects on B cells and IFN signaling,7 these data demonstrate targeted effects of DZP on T cell activation, antigen presentation, and proinflammatory cytokines, such as IFN-γ, involved in adaptive immune responses related to SLE. These findings support the broad mechanism of action of DZP in modulating multiple aspects of SLE immunopathology."

IO biomarker • P2b data • PK/PD data • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CCL19 • CD40LG • CXCL9 • IFNG • IL12B • TNFA • TNFRSF9

Dapirolizumab Pegol Phase 3 Data Presented at the American College of Rheumatology Shows Significant Reduction in Systemic Lupus Erythematosus Disease Activity (GlobeNewswire) - P3 | N=321 | PHOENYCS GO (NCT04294667) | Sponsor: UCB Biopharma SRL | "UCB...and Biogen Inc...today presented detailed results from the Phase 3 PHOENYCS GO study evaluating dapirolizumab pegol (DZP)...demonstrating significant clinical improvement in disease activity in people living with moderate-to-severe systemic lupus erythematosus (SLE). The results were shared during an oral, late-breaker presentation at ACR Convergence 2024, the American College of Rheumatology’s annual meeting, in Washington, DC....On the primary endpoint measuring improvement of moderate-to-severe disease activity as assessed by achievement of British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) after 48 weeks, study participants receiving DZP plus SOC had a statistically significant 14.6% (95% confidence interval [CI]: 3.3, 25.8; p=0.0110) higher response rate (49.5%) than those receiving SOC alone (34.6%)."

P3 data • Immunology • Lupus • Systemic Lupus Erythematosus

Lupus Research Alliance Announces Lupus Research Highlights at ACR Convergence 2024 (PRNewswire) - "The Lupus Research Alliance (LRA), the largest private funder of lupus research worldwide, today announced that a total of 33 studies, funded by the organization or supported by its clinical research affiliate Lupus Therapeutics, will be presented at ACR Convergence 2024. The annual meeting of the American College of Rheumatology takes place November 14-19, at the Walter E. Washington Convention Center in Washington, D.C."

Clinical data • Lupus • Lupus Nephritis • Systemic Lupus Erythematosus