frexalimab (SAR441344) / ImmuNext, Sanofi, Royalty - LARVOL DELTA

Long-term Treatment Effects of Frexalimab on NfL, CXCL13, and Brain Volume Loss in Relapsing Multiple Sclerosis (EAN 2026) - P2 | "Three years of frexalimab treatment markedly reduced NfL and CXCL13, and limited BVL in pwRMS. These data demonstrate its effects on neuroinflammation and neurodegeneration, supporting further investigation in RMS and non-relapsing secondary progressive MS."

CNS Disorders • Inflammation • Multiple Sclerosis • CD40LG • CXCL13 • NEFL • Plasma NfL

Efficacy and safety of Frexalimab in participants with relapsing multiple sclerosis: 3-year results from the phase 2 open-label extension (EAN 2026) - P2 | "Frexalimab continues to exert sustained reduction in disease activity with favourable safety in pwRMS over 3 years, supporting its further development in phase-3 trials for RMS (FREXALT) and non-relapsing secondary progressive MS (FREVIVA) as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • P2 data • CNS Disorders • Multiple Sclerosis • CD40LG

Long-term Frexalimab Treatment Modulates the Activity of Immune Networks (EAN 2026) - P2 | "Long-term frexalimab treatment exerts comprehensive immunomodulatory effects by downregulating inflammatory mediators associated with disease progression. These findings support understanding of frexalimab's mechanism of action, which targets immune networks involving adaptive and innate immunity, and holds the potential to mitigate acute and chronic neuroinflammation in MS."

IO biomarker • CNS Disorders • Inflammation • Multiple Sclerosis • CD27 • CD40LG • CSF1R • CXCL13 • GZMA

Frexalimab in Preservation of Endogenous Insulin Secretion Compared to Placebo in Adults, Adolescents and Children on Top of Insulin Therapy (FABULINUS) (clinicaltrials.gov) - P2 | N=197 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Frexalimab, a Second-Generation Anti-CD40 Ligand Antibody: Prolonged Kidney Allograft Survival in Non-Human Primates with Subcutaneous Maintenance Administration (ATC 2026) - "These data demonstrate that frexalimab, an anti-CD40L, without other immunosuppressive agents, is effective and safe at preventing rejection in a NHP transplantation model. This supports the advancement of frexalimab's clinical development program in kidney transplantation."

Clinical • Cardiovascular • CNS Disorders • Cytomegalovirus Infection • Diabetes • Glomerulonephritis • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Multiple Sclerosis • Nephrology • Systemic Lupus Erythematosus • Type 1 Diabetes Mellitus • CD40LG

Subcutaneous Administration of Frexalimab In Relapsing Multiple Sclerosis and Non-Relapsing Secondary Progressive Multiple Sclerosis: Design of the phase 3 Frexcite Trial (CMSC 2026) - P2, P3 | "This FREXCITE Phase 3 bridging study will assess the PK non-inferiority, safety, efficacy, and patient experience of frexalimab administered SC using OBDS compared to IV administration in participants with RMS and nrSPMS, supporting a more convenient route of administration for those requiring long-term frexalimab therapy."

P3 data • CNS Disorders • Multiple Sclerosis • CD40LG

Frexadigital AI Substudy: AI-Based Smartphone Video Assessments of Motor Function In RMS and Non-Relapsing SPMS Population (CMSC 2026) - P3 | " FREXADIGITAL AI is an optional exploratory substudy of the phase 3 FREXALT (RMS) and FREVIVA (nrSPMS) studies comparing the efficacy and safety of frexalimab to teriflunomide (FREXALT, NCT06141473) and/or placebo (FREVIVA, NCT06141486) over 24 months. This innovative approach offers a non-invasive, patient-centric, objective, standardized, and accessible method to estimate disease progression and treatment efficacy in people with MS."

Clinical • Video • CNS Disorders • Multiple Sclerosis

Efficacy and Safety of Frexalimab In Participants with Relapsing Multiple Sclerosis: 3-Year Results from the Phase 2 Open-Label Extension (CMSC 2026) - P2 | "Frexalimab continues to exert sustained reduction in disease activity with favourable safety in pwRMS through 3 years, supporting its further development in phase 3 trials (FREXALT and FREVIVA) as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • P2 data • CNS Disorders • Multiple Sclerosis • CD40LG

At the Consortium of Multiple Sclerosis Centers (CMSC) 2026 Annual Meeting, researchers unveiled highly anticipated 3-year results from the phase 2 open-label extension of frexalimab, an investigational treatment for relapsing multiple sclerosis (RMS). (Pharmacy Times) - "The clinical outcomes were equally robust. In the group receiving 1200 mg intravenously (IV), 86% of participants remained relapse-free over 3 years. The adjusted annualized relapse rate (ARR) for this group was remarkably low at 0.11. Furthermore, participants’ physical disability levels, measured by the Expanded Disability Status Scale, remained stable through week 144...A key focus of the presentation was frexalimab’s safety profile, particularly its impact on the immune system. Because the drug does not deplete lymphocytes, mean lymphocyte counts remained stable over the 144-week duration. Additionally, levels of protective antibodies—immunoglobulin G (IgG) and M (IgM)—showed stability or only marginal decreases, which is a significant finding for long-term immune health."

P2 data • Immunology • Multiple Sclerosis

A Phase 2 Trial of Frexalimab, a CD40L Antagonist, in Adolescents and Adults With Recent-Onset Type 1 Diabetes (FABULINUS): Rationale and Study Design. (PubMed, Diabetes Obes Metab) - P2 | "The results will be submitted to a peer-reviewed medical journal and presented at conferences. EU trial number: 2022-500531-36-00 and ClinicalTrials.gov: NCT06111586."

Journal • P2 data • Diabetes • Hypoglycemia • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus • CD40LG

FREVIVA: Efficacy and Safety Study of Frexalimab (SAR441344) in Adults With Nonrelapsing Secondary Progressive Multiple Sclerosis (clinicaltrials.gov) - P3 | N=943 | Active, not recruiting | Sponsor: Sanofi | Trial primary completion date: Dec 2026 ➔ Mar 2028 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial primary completion date • CNS Disorders • Multiple Sclerosis • Plasma NfL

FREXALT: Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis (clinicaltrials.gov) - P3 | N=1655 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis • Plasma NfL

EFC18554: A study to investigate the efficacy and safety of frexalimab versus tacrolimus in adults undergoing kidney transplantation (clinicaltrialsregister.eu) - P2/3 | N=269 | Recruiting | Sponsor: Sanofi-Aventis Recherche & Developpement

New P2/3 trial • Immunology • Transplant Rejection • Transplantation

Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis (clinicaltrials.gov) - P3 | N=67 | Recruiting | Sponsor: Sanofi | N=41 ➔ 67

Enrollment change • Head-to-Head • CNS Disorders • Multiple Sclerosis

FREXADIGITAL AI Substudy: AI-based Smartphone Video Assessments of Motor Function in RMS and nrSPMS Population (AAN 2026) - P3 | "Design/Methods FREXADIGITAL AI is an optional exploratory substudy of the phase 3 FREXALT (RMS) and FREVIVA (nrSPMS) studies comparing the efficacy and safety of frexalimab to teriflunomide (FREXALT, NCT06141473) and/or placebo (FREVIVA, NCT06141486) over 24 months. The main results are expected at study completion. Conclusions This innovative approach offers a non-invasive, patient-centric, objective, standardized, and accessible method to estimate disease progression and treatment efficacy in people with MS."

Clinical • Video • CNS Disorders • Multiple Sclerosis

Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis (clinicaltrials.gov) - P3 | N=41 | Recruiting | Sponsor: Sanofi | N=20 ➔ 41

Enrollment change • Head-to-Head • CNS Disorders • Multiple Sclerosis

Long-term Treatment Effects of Frexalimab on NfL, CXCL13, and Brain Volume Loss in Relapsing Multiple Sclerosis (AAN 2026) - P2 | "In the IV arm (Phase 3 dose), BVL from baseline was -0.84% (IQR: -1.14 to -0.50) for whole brain, -1.18% (-1.85 to -0.13) for thalamus, and -0.85% (-1.67 to -0.39) for cerebral cortex. Conclusions Three years of frexalimab treatment demonstrated marked reductions in NfL and CXCL13, and limited BVL in pwRMS. These data contribute to understanding the effect of frexalimab on neuroinflammation and neurodegeneration, and support further investigations in both RMS and non-relapsing secondary progressive MS."

CNS Disorders • Inflammation • Multiple Sclerosis • CD40LG • CXCL13 • NEFL • Plasma NfL

Non-inferiority Study of Frexalimab Subcutaneous Administration Compared to Intravenous Administration in Adult Participants With Multiple Sclerosis (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Sanofi | N=67 ➔ 160

Enrollment change • Head-to-Head • Trial initiation date • CNS Disorders • Multiple Sclerosis

Efficacy and Safety of Frexalimab in Participants With Relapsing Multiple Sclerosis: Three-year Results From the Phase Two Open-label Extension (AAN 2026) - P2 | "Frexalimab was well-tolerated through W144, with no new safety signals, stable lymphocyte counts and immunoglobulin levels. Conclusions Frexalimab continues to exert sustained reduction in disease activity with favourable safety in pwRMS through 3 years, supporting its further development in phase 3 trials (FREXALT and FREVIVA) as a potential high-efficacy, non-lymphocyte-depleting therapy."

Clinical • CNS Disorders • Multiple Sclerosis • CD40LG

EFC18098: Non-inferiority study of frexalimab subcutaneous administration compared to intravenous administration in adult participants with multiple sclerosis. (clinicaltrialsregister.eu) - P2/3 | N=20 | Not yet recruiting | Sponsor: Sanofi-Aventis Recherche & Developpement

Head-to-Head • New P2/3 trial • CNS Disorders • Multiple Sclerosis

FREXERA: A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation (clinicaltrials.gov) - P2/3 | N=526 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Transplant Rejection • Transplantation

APATURA: Efficacy and Safety of Frexalimab (SAR441344) in the Treatment of Systemic Lupus Erythematosus (clinicaltrials.gov) - P2 | N=109 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

Psychometric validation of PROMIS-Fatigue-MS-8a and MSIS-29v2 questionnaires in relapsing multiple sclerosis participants enrolled in a phase 2 trial of frexalimab. (PubMed, Mult Scler Relat Disord) - P2 | "PROMIS-Fatigue-MS-8a and MSIS-29v2 are valid and reliable measures for evaluating treatment benefits in clinical trials of RMS."

Journal • P2 data • CNS Disorders • Fatigue • Multiple Sclerosis

FREXERA: A Study to Investigate the Efficacy and Safety of Frexalimab Versus Tacrolimus in Adults Undergoing Kidney Transplantation (clinicaltrials.gov) - P2/3 | N=526 | Not yet recruiting | Sponsor: Sanofi

New P2/3 trial • Immunology • Transplant Rejection • Transplantation

Frexalimab in Relapsing Multiple Sclerosis and Non-Relapsing Secondary Progressive Multiple Sclerosis: Design of the Phase 3 FREXCITE Trial (ACTRIMS Forum 2026) - P2, P3 | "This FREXCITE Phase 3 bridging study will assess the PK non-inferiority, safety, efficacy, and patient experience of frexalimab administered SC using OBDS compared to IV administration in participants with RMS and nrSPMS, supporting a more convenient route of administration for those requiring long-term frexalimab therapy."

P3 data • CNS Disorders • Inflammation • Multiple Sclerosis • CD40LG