--- title: "Frexalimab | PepTracker Pro" url: https://peptrackerpro.com/peptides/frexalimab description: "Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator." lang: en --- Skip to main content **Educational information only.** This site does not provide medical advice. Read full disclaimer (https://peptrackerpro.com/disclaimer) **Research-only content.** This page is for educational purposes and does not constitute medical advice. Read full disclaimer → (https://peptrackerpro.com/research-disclaimer) # Frexalimab High Evidence Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator. Aliases Frexalimab +7 more Evidence High Evidence Last Updated 2026-09-25 Reading Time 9 min ## What It Is Frexalimab (development code SAR441344) is a fully human, second-generation monoclonal antibody that targets CD40 ligand (CD40L, also known as CD154 or TNFSF5). CD40L is expressed mainly on activated T cells and platelets; its receptor CD40 sits on B cells, dendritic cells, macrophages and other antigen-presenting cells. The CD40-CD40L interaction is a central costimulatory axis of adaptive immunity - it licenses dendritic cells, drives B-cell activation, germinal-center formation, antibody class switching and the generation of memory, and sustains T-cell help. By binding CD40L, frexalimab blocks that costimulatory signal and is designed to quiet a broad, antibody- and T-cell-driven autoimmune program without depleting the immune cells themselves. This upstream, non-depleting position is the conceptual pitch: interrupting a shared costimulatory checkpoint may dampen several arms of autoimmunity at once while preserving the immune repertoire. Blocking CD40L has been an attractive immunology target since the 1990s, but the first-generation anti-CD40L antibodies caused thromboembolic (blood-clot) events because their Fc region engaged Fc-gamma-receptor IIa on platelets and triggered platelet aggregation. Frexalimab is a second-generation antibody engineered with a modified Fc region that does not activate platelets, and no thromboembolic safety signal has emerged in its trials so far. The lead indication is relapsing multiple sclerosis (RMS) in adults, with a parallel program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS study (NCT04879628), 129 adults were randomized to higher-dose intravenous frexalimab (1200 mg every 4 weeks after an 1800 mg loading dose; n=52), lower-dose subcutaneous frexalimab (300 mg every 2 weeks after a 600 mg loading dose; n=51), or matching placebo (n=26). The primary endpoint - the number of new gadolinium-enhancing T1 brain lesions at week 12 - fell by 89% in the higher-dose arm (rate ratio 0.11; 95% CI 0.03-0.38) and 79% in the lower-dose arm (rate ratio 0.21; 95% CI 0.08-0.56) versus placebo; the drug was well tolerated, with COVID-19 and headache the most common adverse events and 97% of participants completing the study. The results were published in the New England Journal of Medicine in 2024. In the open-label extension, roughly 96% of higher-dose participants were free of gadolinium-enhancing lesions at week 48, blood neurofilament light (a marker of nerve-cell damage) declined, and data presented through 2025-2026 (AAN 2025 two-year and CMSC 2026 three-year readouts) showed the low disease activity was durable. Frexalimab has now advanced into a large Phase 3 MS program: FREXALT (two independent studies under a master protocol, NCT06141473, comparing frexalimab with oral teriflunomide in relapsing MS, roughly 700 patients each) and FREVIVA (NCT06141486, comparing frexalimab with placebo in nonrelapsing secondary progressive MS, about 858 patients), with a bridging study (FREXCITE) evaluating a subcutaneous on-body delivery system against the intravenous formulation. Beyond MS, frexalimab is being studied in recent-onset type 1 diabetes (the Phase 2 FABULINUS trial, NCT06111586, testing whether CD40L blockade can preserve insulin-producing beta cells) and in systemic lupus erythematosus, both riding on the same costimulation-blocking rationale. A Phase 2 study in Sjogren's syndrome was discontinued in 2024 after it confirmed the drug's activity and safety but did not reach its efficacy endpoint. Frexalimab is investigational and is not approved by the FDA or any other regulator for MS or any other condition; it originated from ImmuNext and is being developed by Sanofi as one of the more valuable assets in its immunology and neurology pipeline. Also known as: Frexalimab, SAR441344, anti-CD40L monoclonal antibody, anti-CD40 ligand antibody, CD40L antagonist, CD154 blocker, second-generation anti-CD40L (Sanofi), frexalimab-Sanofi ## Why Researchers Study It Researchers study frexalimab because it revives one of immunology's most attractive but long-stalled targets. Blocking CD40 ligand interrupts a master costimulatory switch that helps activate B cells and antigen-presenting cells, drives antibody production and germinal-center reactions, and sustains the T-cell help behind many autoimmune diseases - so a single antibody could, in principle, calm several arms of autoimmunity at once without depleting immune cells. That promise was recognized in the 1990s, but the first-generation anti-CD40L antibodies caused dangerous blood clots because their Fc tails activated platelets, and the whole approach was shelved. Frexalimab is a second-generation antibody re-engineered so its Fc region no longer triggers platelets, and its Phase 2 multiple sclerosis data - an 89% reduction in new gadolinium-enhancing brain lesions with sustained control out to three years and falling neurofilament light - suggest the target can be hit safely and powerfully. The appeal is threefold: a broad, upstream, non-depleting mechanism distinct from cytokine-specific biologics and from the OX40-OX40L blockade of amlitelimab; potential activity across very different diseases (relapsing and progressive MS, recent-onset type 1 diabetes, systemic lupus); and, in progressive MS, a shot at a patient population where almost nothing works. The mixed signal from a discontinued Sjogren's study keeps expectations grounded and makes the Phase 3 FREXALT and FREVIVA outcomes some of the most closely watched readouts in neuroimmunology. ## Proposed Mechanisms - CD40 ligand (CD40L/CD154/TNFSF5) blockade: frexalimab binds CD40L on activated T cells and platelets and prevents it from engaging CD40 on B cells and antigen-presenting cells, interrupting a central costimulatory 'second signal.' - Broad dampening of adaptive autoimmunity: blocking CD40-CD40L reduces B-cell activation, germinal-center formation, antibody class switching and memory generation, and blunts dendritic-cell licensing and T-cell help across multiple autoimmune programs rather than neutralizing a single cytokine. - Non-depleting, non-cytotoxic design: frexalimab modulates immune activation without killing B cells or T cells, aiming to preserve the immune repertoire while reducing pathological signaling. - Re-engineered Fc region to avoid platelet activation: unlike first-generation anti-CD40L antibodies that engaged Fc-gamma-receptor IIa on platelets and caused thromboembolism, frexalimab's Fc is modified so it does not activate platelets - the key safety innovation that made the target usable again. - Effect on nerve-cell damage in MS: by suppressing new inflammatory (gadolinium-enhancing) lesions and lowering blood neurofilament light, frexalimab is proposed to reduce ongoing central-nervous-system injury, with durability seen in open-label extension data. - Platform potential across immune-mediated diseases: the same upstream costimulation-blocking rationale underpins parallel programs in nonrelapsing secondary progressive MS, recent-onset type 1 diabetes (preserving beta-cell function) and systemic lupus erythematosus. ## Evidence Snapshot High Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Phase 2 randomized, double-blind, placebo-controlled trial (NCT04879628) in adults with relapsing multiple sclerosis; primary results published in the New England Journal of Medicine (2024). | 129 adults with relapsing MS randomized to higher-dose intravenous frexalimab (1200 mg every 4 weeks after an 1800 mg loading dose; n=52), lower-dose subcutaneous frexalimab (300 mg every 2 weeks after a 600 mg loading dose; n=51), or placebo (n=26). | New gadolinium-enhancing T1 brain lesions at week 12 fell by 89% (higher dose; rate ratio 0.11, 95% CI 0.03-0.38) and 79% (lower dose; rate ratio 0.21, 95% CI 0.08-0.56) versus placebo. The antibody was well tolerated - COVID-19 and headache were the most common adverse events, no thromboembolic signal emerged, and 97% of participants completed the study - establishing proof of concept for safe, potent CD40L blockade. | Source | | Open-label long-term extension of the Phase 2 relapsing-MS trial, with data reported at 48 weeks (2024), two years (AAN 2025) and three years (CMSC 2026). | Participants continuing frexalimab from the Phase 2 study, followed with serial MRI and blood biomarkers. | About 96% of higher-dose participants were free of gadolinium-enhancing lesions at week 48; blood neurofilament light (a marker of nerve-cell damage) declined; and low disease activity was maintained through two and three years, supporting durability and the move to Phase 3. | Source | | Phase 3 pivotal program: FREXALT (two independent studies under master protocol NCT06141473) and FREVIVA (NCT06141486), plus the FREXCITE delivery bridging study. | FREXALT compares frexalimab with oral teriflunomide in relapsing MS (about 700 patients per study); FREVIVA compares frexalimab with placebo in nonrelapsing secondary progressive MS (about 858 patients); FREXCITE tests a subcutaneous on-body delivery system against the intravenous formulation. | Ongoing. Designed to confirm that frexalimab reduces clinical relapses and slows disability progression - including in progressive MS, where treatment options are scarce - against an active comparator, and to establish long-term safety at scale. Readouts are among the most closely watched in neuroimmunology. | Source | | Phase 2 trials in other autoimmune diseases: FABULINUS in recent-onset type 1 diabetes (NCT06111586) and a systemic lupus erythematosus program; a Sjogren's syndrome study (discontinued 2024). | FABULINUS enrolls adolescents and adults with recent-onset type 1 diabetes on top of insulin therapy to test preservation of endogenous insulin (C-peptide); parallel mid-stage work in systemic lupus erythematosus. | Investigational and unproven outside MS. The type 1 diabetes and lupus programs test whether upstream CD40L blockade translates to other autoimmune diseases, while the discontinued Sjogren's study - which confirmed activity and safety but missed its efficacy endpoint - shows the mechanism does not work equally everywhere. | Source | ## Commonly Discussed Benefits Immune Modulation: https://peptrackerpro.com/benefits/immune-modulation Inflammation: https://peptrackerpro.com/benefits/inflammation autoimmune: https://peptrackerpro.com/benefits/autoimmune Disease Modification: https://peptrackerpro.com/benefits/disease-modification Researching Frexalimab? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=frexalimab) ## Safety & Cautions - Frexalimab is an investigational biologic that is NOT approved by the FDA or any regulator for multiple sclerosis, type 1 diabetes, lupus or any other condition. It is studied only within clinical trials under medical supervision; any product sold as 'frexalimab' or 'SAR441344' outside a legitimate trial is unverified and should not be used. - The whole history of this drug class is defined by a safety problem: first-generation anti-CD40L antibodies caused serious thromboembolic (blood-clot) events because their Fc region activated platelets. Frexalimab is specifically engineered to avoid that, and no thromboembolic signal has appeared in its trials, but long-term, large-scale safety confirmation is exactly what the Phase 3 program is designed to provide. - As an immunomodulatory antibody that dampens a central costimulation pathway, class-level considerations include a theoretical risk of infection and potentially blunted responses to vaccines. In the Phase 2 MS trial the most common adverse events were COVID-19 (generally mild-to-moderate) and headache; long-term immune-safety data are still accumulating. - Efficacy in MS to date rests mainly on an MRI biomarker (new gadolinium-enhancing lesions) and open-label extensions; the definitive test of whether frexalimab reduces relapses and disability progression - and how it compares with an active oral comparator (teriflunomide) - depends on the ongoing Phase 3 FREXALT and FREVIVA readouts. - Results have not been uniform across indications: a Phase 2 study in Sjogren's syndrome was discontinued in 2024 after it fell short on efficacy, a reminder that upstream costimulation blockade does not work equally in every autoimmune disease and that the type 1 diabetes and lupus programs remain unproven. ## Comparisons See how Frexalimab compares to related peptides: Frexalimab vs Efgartigimod: https://peptrackerpro.com/compare/frexalimab-vs-efgartigimod Frexalimab vs Nipocalimab: https://peptrackerpro.com/compare/frexalimab-vs-nipocalimab Frexalimab vs Rozanolixizumab: https://peptrackerpro.com/compare/frexalimab-vs-rozanolixizumab Frexalimab vs Povetacicept: https://peptrackerpro.com/compare/frexalimab-vs-povetacicept Frexalimab vs Amlitelimab: https://peptrackerpro.com/compare/frexalimab-vs-amlitelimab Frexalimab vs Rocatinlimab: https://peptrackerpro.com/compare/frexalimab-vs-rocatinlimab Frexalimab vs Atacicept: https://peptrackerpro.com/compare/frexalimab-vs-atacicept ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Inhibition of CD40L with Frexalimab in Multiple Sclerosis - New England Journal of Medicine (2024) PubMed (https://www.nejm.org/doi/full/10.1056/NEJMoa2309439) 2. [2] Phase 2 data published in NEJM show potential of frexalimab as high-efficacy therapy in relapsing MS (February 2024) - Sanofi PubMed (https://www.sanofi.com/en/media-room/press-releases/2024/2024-02-15-13-00-00-2829933) 3. [3] New 48-week frexalimab Phase 2 data support potential for high sustained efficacy in multiple sclerosis (April 2024) - Sanofi PubMed (https://www.sanofi.com/en/media-room/press-releases/2024/2024-04-17-05-00-00-2864225) 4. [4] Efficacy and Safety Studies of Frexalimab (SAR441344) in Adults With Relapsing Forms of Multiple Sclerosis (FREXALT master protocol) - ClinicalTrials.gov NCT06141473 PubMed (https://clinicaltrials.gov/study/NCT06141473) 5. [5] Efficacy and Safety Study of Frexalimab (SAR441344) in Adults With Nonrelapsing Secondary Progressive Multiple Sclerosis (FREVIVA) - ClinicalTrials.gov NCT06141486 / Sanofi PubMed (https://www.sanofi.com/en/clinical-trials/nct06141486) 6. [6] A Phase 2 Trial of Frexalimab, a CD40L Antagonist, in Adolescents and Adults With Recent-Onset Type 1 Diabetes (FABULINUS): Rationale and Study Design - Diabetes, Obesity and Metabolism (2026) PubMed (https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.70785) 7. [7] Sanofi crosses Sjogren's off frexalimab's hit list after Phase 2 data disappoint (2024) - Fierce Biotech PubMed (https://www.fiercebiotech.com/biotech/sanofi-crosses-sjogrens-5b-drugs-hit-list-after-phase-2-data-disappoint) 8. [8] CMSC 2026: trial data show frexalimab benefits lasting 3 years in relapsing MS - Multiple Sclerosis News Today PubMed (https://multiplesclerosisnewstoday.com/news-posts/2026/06/01/cmsc-2026-trial-data-show-frexalimab-benefits-lasting-3-years/) ### Keep researching in the app - Log Frexalimab to your private tracker - Set a dosing reminder - Compare it side-by-side with your stack Open PepTracker Pro Free: https://app.peptrackerpro.com/?add=frexalimab Browse more peptides: https://peptrackerpro.com/peptides ## Related Peptides ### Efgartigimod High Evidence Efgartigimod (efgartigimod alfa, brand names Vyvgart intravenous and Vyvgart Hytrulo subcutaneous) is a first-in-class antagonist of the neonatal Fc receptor (FcRn) developed by argenx as ARGX-113. It is not a small synthetic peptide but an engineered fragment of the human immunoglobulin G1 (IgG1) antibody - specifically the Fc portion that normally binds FcRn - modified with argenx's ABDEG technology to bind FcRn with much higher affinity than natural IgG at both neutral and acidic pH. FcRn is the salvage receptor that rescues circulating IgG from lysosomal degradation and recycles it back into the blood, giving antibodies their long half-life. By outcompeting endogenous IgG for FcRn, efgartigimod blocks that recycling and drives rapid clearance of IgG - including the pathogenic autoantibodies that cause many autoimmune diseases - typically lowering total IgG by roughly 60-70% within weeks, without reducing IgM, IgA, or albumin. It was the first FcRn blocker ever approved: FDA-approved in December 2021 (Vyvgart IV) for acetylcholine-receptor-antibody-positive generalized myasthenia gravis (gMG) on the strength of the Phase 3 ADAPT trial, followed by a subcutaneous co-formulation with recombinant hyaluronidase (Vyvgart Hytrulo) for gMG in 2023 and for chronic inflammatory demyelinating polyneuropathy (CIDP) in 2024. In May 2026 the FDA expanded the gMG label to all serotypes - including AChR-antibody-negative (seronegative) patients - based on the Phase 3 ADAPT SERON trial, making efgartigimod the first and only therapy approved across every gMG antibody subtype. It is being studied in a broad set of other IgG-driven autoimmune diseases, including primary immune thrombocytopenia, myositis, Sjogren's disease, bullous pemphigoid, and lupus nephritis. Immune Modulation: https://peptrackerpro.com/benefits/immune-modulation Neuromuscular Function: https://peptrackerpro.com/benefits/neuromuscular-function Rare Disease Treatment: https://peptrackerpro.com/benefits/rare-disease-treatment Disease Modification: https://peptrackerpro.com/benefits/disease-modification View Details: https://peptrackerpro.com/peptides/efgartigimod \+ Compare: https://peptrackerpro.com/compare?select=efgartigimod Track in App: https://app.peptrackerpro.com/?add=efgartigimod ### Nipocalimab High Evidence Nipocalimab (brand name Imaavy, development code M281) is a fully human, aglycosylated, 'effectorless' IgG1 monoclonal antibody that blocks the neonatal Fc receptor (FcRn), developed by Johnson & Johnson (Janssen). Like efgartigimod it lowers circulating immunoglobulin G (IgG) - including the pathogenic autoantibodies that drive many autoimmune diseases - by occupying FcRn and preventing it from recycling IgG back into the blood, so unrescued IgG is routed to the lysosome and degraded, typically cutting total IgG by roughly 65-75% while sparing IgM, IgA, complement, and albumin. Unlike efgartigimod's engineered Fc fragment, nipocalimab is a full-length monoclonal antibody engineered to be aglycosylated and effectorless (it does not trigger ADCC or complement-dependent cytotoxicity), and it is dosed as a maintenance intravenous infusion for continuous IgG suppression rather than in short cycles. The FDA approved Imaavy on April 30, 2025 for generalized myasthenia gravis (gMG) in anti-AChR-antibody-positive and anti-MuSK-antibody-positive patients aged 12 and older - making it the first FcRn blocker approved for adolescents and the first to explicitly cover MuSK-positive disease - on the strength of the Phase 3 Vivacity-MG3 trial. It has since generated positive data across a striking breadth of IgG-mediated conditions: Sjogren's disease (Phase 2 DAHLIAS), rheumatoid arthritis, warm autoimmune hemolytic anemia (wAIHA), and - uniquely among FcRn blockers - maternal-fetal alloimmune disease, where it is being developed to treat hemolytic disease of the fetus and newborn (HDFN) by crossing the placenta to protect the fetus. In April 2026 the FDA granted Priority Review to nipocalimab for wAIHA, positioning it as a potential first approved therapy for that condition. View Details: https://peptrackerpro.com/peptides/nipocalimab \+ Compare: https://peptrackerpro.com/compare?select=nipocalimab Track in App: https://app.peptrackerpro.com/?add=nipocalimab ### Rozanolixizumab High Evidence Rozanolixizumab (brand name Rystiggo, development code UCB7665) is a humanized IgG4 monoclonal antibody that blocks the neonatal Fc receptor (FcRn), developed by UCB. Like efgartigimod and nipocalimab it lowers circulating immunoglobulin G (IgG) - including the pathogenic autoantibodies that drive many autoimmune diseases - by binding FcRn and preventing it from recycling IgG back into the blood, so unrescued IgG is routed to the lysosome and degraded, typically cutting total IgG by roughly 70-80% while sparing IgM, IgA, complement, and albumin. Unlike efgartigimod's engineered Fc fragment, rozanolixizumab is a full-length humanized antibody, and unlike nipocalimab's intravenous infusion it is given as a rapid subcutaneous infusion (including via an on-body delivery device), typically in weekly cycles that are repeated based on clinical response rather than continuously. The FDA approved Rystiggo on June 27, 2023 for generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine-receptor (AChR) antibody-positive or anti-muscle-specific-tyrosine-kinase (MuSK) antibody-positive - making it the first therapy ever approved to treat both of those gMG subtypes - on the strength of the Phase 3 MycarinG trial. It has since been studied across other IgG-mediated diseases, including chronic inflammatory demyelinating polyneuropathy (CIDP), where it did not show meaningful benefit and was not advanced to Phase 3, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), primary immune thrombocytopenia (ITP), and other autoantibody conditions where development continues. The European Medicines Agency approved rozanolixizumab in January 2024 and the UK MHRA in March 2024. View Details: https://peptrackerpro.com/peptides/rozanolixizumab \+ Compare: https://peptrackerpro.com/compare?select=rozanolixizumab Track in App: https://app.peptrackerpro.com/?add=rozanolixizumab ### Povetacicept High Evidence Povetacicept (development code ALPN-303) is an investigational, once-monthly, subcutaneously injected recombinant fusion protein that simultaneously blocks two B-cell survival signals - BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). It is built from an engineered ('variant') form of the natural TACI receptor's extracellular domain fused to an antibody (IgG) Fc region, so it acts as a high-affinity decoy that soaks up both BAFF and APRIL before they can reach their receptors on B cells and plasma cells. Because BAFF and APRIL drive the maturation and antibody production of the immune cells behind many autoantibody- and immune-complex-mediated diseases, povetacicept is being developed for B-cell-driven autoimmune conditions - most prominently IgA nephropathy (IgAN), where APRIL fuels the production of the galactose-deficient IgA1 that damages the kidney. Originated by Alpine Immune Sciences (acquired by Vertex Pharmaceuticals in 2024), povetacicept has received FDA Breakthrough Therapy Designation for IgAN; in March 2026 the Phase 3 RAINIER trial reported a positive prespecified Week 36 interim analysis (a ~52% reduction in urine protein-to-creatinine ratio from baseline and a ~50% reduction versus placebo), and in June 2026 the FDA accepted a Biologics License Application for accelerated approval with a target action date of November 30, 2026. Povetacicept is an experimental biologic given only in clinical trials; it is not a supplement, nootropic, or research chemical. renal: https://peptrackerpro.com/benefits/renal autoimmune: https://peptrackerpro.com/benefits/autoimmune Disease Modification: https://peptrackerpro.com/benefits/disease-modification B-cell-modulation: https://peptrackerpro.com/benefits/B-cell-modulation View Details: https://peptrackerpro.com/peptides/povetacicept \+ Compare: https://peptrackerpro.com/compare?select=povetacicept Track in App: https://app.peptrackerpro.com/?add=povetacicept ### Amlitelimab High Evidence Amlitelimab (SAR445229, formerly KY1005) is a fully human, non-T-cell-depleting monoclonal antibody from Sanofi that blocks OX40 ligand (OX40L), a costimulatory signal that drives and sustains T-cell-mediated inflammation. Rather than neutralizing a single cytokine like IL-4/IL-13 (dupilumab) or IL-5 (depemokimab), amlitelimab acts upstream at the OX40-OX40L checkpoint to dampen a broad, memory-driven inflammatory program without depleting T cells. Its lead (anchor) indication is moderate-to-severe atopic dermatitis in people aged 12 and older, where a distinctive feature is very infrequent dosing: after a loading dose it is given subcutaneously as little as four times a year (every 12 weeks). In the Phase 3 program - COAST 1, COAST 2 and SHORE - amlitelimab met its primary endpoints with EASI-75 and vIGA-AD 0/1 responses that increased over time, though COAST 2's absolute response rates were more modest and some observers called that readout mixed. Amlitelimab is investigational and not yet approved by any regulator; Sanofi originally gained it through its ~$1.1B acquisition of Kymab in 2021. Inflammation: https://peptrackerpro.com/benefits/inflammation Immune Modulation: https://peptrackerpro.com/benefits/immune-modulation Skin: https://peptrackerpro.com/benefits/skin type-2-inflammation: https://peptrackerpro.com/benefits/type-2-inflammation View Details: https://peptrackerpro.com/peptides/amlitelimab \+ Compare: https://peptrackerpro.com/compare?select=amlitelimab Track in App: https://app.peptrackerpro.com/?add=amlitelimab ### Rocatinlimab High Evidence Rocatinlimab (AMG 451 / KHK4083) is an investigational anti-OX40 monoclonal antibody developed by Kyowa Kirin and Amgen for moderate-to-severe atopic dermatitis (eczema). Unlike amlitelimab, which blocks the OX40 ligand (OX40L) on antigen-presenting cells without depleting cells, rocatinlimab binds the OX40 receptor directly on activated pathogenic T cells and reduces (depletes) them - a 'T-cell rebalancing' approach meant to reset the immune drivers of chronic inflammation rather than continuously neutralize a single cytokine. In the large Phase 3 ROCKET program the drug met its co-primary endpoints: in ROCKET-IGNITE (NCT05398445; 769 adults, added to topical therapy) week-24 EASI-75 reached about 42% (higher dose) and 36% (lower dose) versus roughly 13% on placebo, and vIGA-AD 0/1 reached about 24% and 19%; in the ROCKET-HORIZON monotherapy study (NCT05651711) EASI-75 was about 33% versus 14% on placebo, though the drug showed no superiority over dupilumab. The pooled Phase 3 results were published in The Lancet in 2025. Despite hitting its endpoints, the program then unraveled on two fronts: in January 2026 Amgen ended the collaboration on strategic-portfolio grounds and returned global rights to Kyowa Kirin, and on March 3, 2026 Kyowa Kirin discontinued ALL rocatinlimab clinical trials - across atopic dermatitis, prurigo nodularis and uncontrolled asthma - after a safety review identified cases of Kaposi's sarcoma (one newly confirmed and one suspected, in addition to a previously confirmed case) that suggested a possible mechanistic link to OX40-pathway modulation. Rocatinlimab is investigational, was never approved by any regulator, and its clinical development has been halted. View Details: https://peptrackerpro.com/peptides/rocatinlimab \+ Compare: https://peptrackerpro.com/compare?select=rocatinlimab Track in App: https://app.peptrackerpro.com/?add=rocatinlimab ### Atacicept High Evidence Atacicept (brand name Trutakna) is a recombinant soluble TACI-Fc fusion protein and the first dual BAFF/APRIL inhibitor approved for IgA nephropathy (IgAN). It fuses the extracellular ligand-binding domain of the TACI receptor to the Fc region of human IgG1, letting it soak up two B-cell survival cytokines at once - BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand). By starving autoreactive B cells and plasma cells of both signals, atacicept lowers production of galactose-deficient IgA1 (Gd-IgA1), the abnormal antibody that drives immune-complex deposition and kidney injury in IgAN. It is given as a 150 mg once-weekly subcutaneous self-injection with an autoinjector at home. On July 7, 2026 the FDA granted atacicept accelerated approval (as Trutakna) to reduce proteinuria in adults with primary IgAN at risk of progression - the first and only BAFF-and-APRIL inhibitor cleared for the disease - based on the Phase 3 ORIGIN 3 trial (NCT04716231, 431 adults), in which it cut urine protein (UPCR) 46% from baseline and 42% versus placebo at week 36 (p<0.0001), reduced Gd-IgA1 by 68%, resolved hematuria in 81% of those with baseline blood in the urine, and produced serious adverse events in only 0.5% of patients (versus 5% on placebo). Originated at ZymoGenetics and developed by Merck KGaA (Merck Serono) before being out-licensed to Vera Therapeutics, atacicept sits alongside the anti-APRIL antibody sibeprenlimab and the engineered dual BAFF/APRIL inhibitor povetacicept in the fast-moving IgAN pipeline. View Details: https://peptrackerpro.com/peptides/atacicept \+ Compare: https://peptrackerpro.com/compare?select=atacicept Track in App: https://app.peptrackerpro.com/?add=atacicept ## Structured data ```json [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Frexalimab", "description": "Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. 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Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. 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Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator." } }, { "@type": "Question", "name": "Clinicians and immunologists comparing upstream costimulation blockers - the CD40-CD40L axis (frexalimab) versus the OX40-OX40L axis (amlitelimab, rocatinlimab) - and how each is being deployed across autoimmune diseases?", "acceptedAnswer": { "@type": "Answer", "text": "Frexalimab is a research peptide studied in preclinical models. Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator." } }, { "@type": "Question", "name": "Endocrinologists and families affected by recent-onset type 1 diabetes interested in the FABULINUS trial and whether blocking CD40L can preserve insulin-producing beta cells?", "acceptedAnswer": { "@type": "Answer", "text": "Frexalimab is a research peptide studied in preclinical models. Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator." } }, { "@type": "Question", "name": "Investors and industry analysts following Sanofi's immunology and neurology pipeline and the value placed on frexalimab (an asset that originated with ImmuNext) as it moves through Phase 3?", "acceptedAnswer": { "@type": "Answer", "text": "Frexalimab is a research peptide studied in preclinical models. Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator." } }, { "@type": "Question", "name": "Readers curious about why anti-CD40L antibodies stalled for two decades over blood-clot risk and how a re-engineered Fc region revived the target?", "acceptedAnswer": { "@type": "Answer", "text": "Frexalimab is a research peptide studied in preclinical models. Frexalimab (SAR441344) is an investigational second-generation, fully human monoclonal antibody from Sanofi that blocks CD40 ligand (CD40L, also called CD154), a costimulatory 'second signal' that helps activate B cells, T cells and antigen-presenting cells and drives adaptive autoimmunity. Rather than depleting immune cells, frexalimab interrupts the CD40-CD40L checkpoint upstream - a mechanism related to but distinct from the OX40-OX40L blockade of amlitelimab. Its lead indication is relapsing multiple sclerosis (RMS), with a second program in nonrelapsing secondary progressive MS (nrSPMS). In the Phase 2 relapsing-MS trial (NCT04879628, published in the New England Journal of Medicine in 2024), frexalimab cut the number of new gadolinium-enhancing brain lesions at week 12 by 89% (higher-dose IV arm) and 79% (lower-dose subcutaneous arm) versus placebo, and open-label extensions out to two and three years show that disease control and reductions in neurofilament light have been sustained. Crucially, frexalimab is engineered so its Fc region does not activate platelets, which is designed to avoid the thromboembolic complications that halted first-generation anti-CD40L antibodies decades ago. It is now in the Phase 3 FREXALT (relapsing MS, versus teriflunomide) and FREVIVA (nrSPMS, versus placebo) trials, with additional Phase 2 programs in type 1 diabetes (FABULINUS) and systemic lupus erythematosus; a Sjogren's syndrome study was discontinued in 2024 after it fell short on efficacy. Frexalimab is investigational and not approved by any regulator." } } ] } ] ```