riliprubart (SAR445088) / Sanofi - LARVOL DELTA

Confirmation of Fixed Quarterly Riliprubart Regimen in Patients with Cold Agglutinin Disease Using Population PK/PD and Exposure-Response Analyses. (PubMed, Clin Pharmacol Ther) - "The observed riliprubart concentration-time profiles from 9 CAD patients were consistently within the popPK simulated 90% prediction interval. Based on the totality of the efficacy, safety, and PK/PD data observed under clinical evaluation, the proposed dose regimen demonstrated suitability for CAD patients."

Journal • PK/PD data • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

LTS: Long-term Safety and Efficacy Study of Riliprubart in Participants With CIDP (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy (S16.009). (PubMed, Neurology) - P2 | "Dr. Hughes has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi."

Journal • P2 data • Fatigue • Infectious Disease • Pain • NEFL • Plasma NfL

Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088 (clinicaltrials.gov) - P1 | N=9 | Terminated | Sponsor: Bioverativ, a Sanofi company | Trial completion date: Jan 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2026 ➔ Mar 2025; Business decision, not related to any safety or efficacy issues.

Trial completion date • Trial primary completion date • Trial termination • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology

Phase 3 Trial Designs Evaluating Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy (AAN 2025) - P2, P3 | "These Phase 3 trials aim to demonstrate efficacy and safety of riliprubart in people with CIDP, including participants with residual disability or refractory disease despite SOC therapies."

P3 data • Pain • NEFL

Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in Chronic Inflammatory Demyelinating Polyneuropathy (AAN 2025) - P2 | "These preliminary results support riliprubart's proof-of-concept in CIDP, with a favorable benefit:risk profile, supporting further investigation as a potential new therapy for people with CIDP who experienced failure/inadequate response to SOC treatments and those with residual disability despite maintenance treatment."

Clinical • P2 data • Fatigue • Infectious Disease • Pain • NEFL • Plasma NfL

LTS: Long-term Safety and Efficacy Study of Riliprubart in Participants With CIDP (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Pain

BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR) (clinicaltrials.gov) - P2 | N=48 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Antibody-mediated Rejection • Immunology • Transplant Rejection • Transplantation

BIVV020 (SAR445088) n Prevention and Treatment of Antibody-mediated Rejection (AMR) (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Sanofi | Trial primary completion date: Nov 2024 ➔ Dec 2025

Trial primary completion date • Antibody-mediated Rejection • Immunology • Transplant Rejection • Transplantation

Autoimmune Hemolytic Anemias: Challenges in Diagnosis and Therapy. (PubMed, Transfus Med Hemother) - "Therapy is quite different, as steroids and rituximab are effective in the former, but have a lower response rate and duration in the latter...Several new drugs are increasingly used or are in trials for relapsed/refractory AIHAs, including B-cell (parsaclisib, ibrutinib, rilzabrutinib), and plasma cell target therapies (bortezomib, daratumumab), bispecific agents (ianalumab, obexelimab, povetacicept), neonatal Fc receptor blockers (nipocalimab), and complement inhibitors (sutimlimab, riliprubart, pegcetacoplan, iptacopan)...Along with all these variables, there are rare forms like mixed (wAIHA plus CAD), atypical (IgA or warm IgM driven), and DAT negative, where the diagnosis and clinical management are particularly challenging. This article covers the classic clinical features, diagnosis, and therapy of wAIHA and CAD, and focuses, with the support of clinical vignettes, on difficult diagnosis and refractory/relapsing cases requiring novel therapies."

Journal • Review • Anemia • Autoimmune Hemolytic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Infectious Disease • Oncology • Rare Diseases • Thrombosis • Transplantation

Psychometric Validation of the Inflammatory-Rasch-Built Overall Disability Scale (I-RODS) and Modified Rasch-Built-Fatigue Severity Scale (R-FSS) in Adult Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (ISPOR-EU 2024) - P2 | "OBJECTIVES: Psychometrically validate and derive meaningful change thresholds for the Inflammatory-Rasch-built Overall Disability Scale (I-RODS) and Modified Rasch-built-Fatigue Severity Scale (R-FSS) using clinical trial data on Riliprubart in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients... I-RODS and R-FSS are acceptable as endpoint measures in clinical trials in adult CIDP patients."

Clinical • CNS Disorders • Depression • Fatigue • Mood Disorders • Pain • Psychiatry

Use of Riliprubart (SAR445088) in cold agglutinin disease (CAD): Interim analysis confirms acceptable efficacy and safety with 12-week intravenous administration in Part 2 of the long-term Phase 1b study (DGHO 2024) - P1 | "These results support 12-weekly IV administration of 3.5 g of riliprubart, with an additional dose on Day 29 after the initial dose, for the Phase 3 study."

Clinical • P1 data • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lymphoma • Lymphoplasmacytic Lymphoma • Meningococcal Infections • Systemic Lupus Erythematosus • Waldenstrom Macroglobulinemia

Pharmacokinetics, pharmacodynamics, safety, and tolerability of a single-dose riliprubart, an anti-C1s humanized monoclonal antibody in East-Asian Adults: results from a phase 1, randomized, open-label trial. (PubMed, Expert Opin Investig Drugs) - "These results are comparable tofirst-in-human study results from non-East-Asian participants and support thesame dosing regimen of riliprubart for global simultaneous clinicaldevelopment. https://cris.nih.go.kr(identifier: KCT0006571)."

Journal • P1 data • PK/PD data

Phase 2 Efficacy and Safety of Riliprubart, a C1s-Complement Inhibitor, in CIDP (EAN 2024) - P2 | "These preliminary results support proof- of- concept for riliprubart in CIDP, with a favourable benefit- risk profile, supporting further investigation in Phase- 3."

Clinical • P2 data • Pain

Two Phase 3 Trial Designs Evaluating Riliprubart, a C1s-Complement Inhibitor, in CIDP (EAN 2024) - P2 | "These Phase 3 trials aim to demonstrate riliprubart efficacy for CIDP, including people with refractory disease or residual disability."

P3 data • Pain

RILIPRUBART (SAR445088) IN COLD AGGLUTININ DISEASE: INTERIM ANALYSIS FROM PART 2 OF A LONG-TERM PHASE 1B TRIAL CONFIRMS ACCEPTABLE EFFICACY AND SAFETY WITH 12-WEEKLY IV ADMINISTRATION (EHA 2024) - P1 | "These safety, efficacy, PK, and PD results support IV administration of 3. 5 g of riliprubart every 12 weeks, withan additional IV infusion on Day 29 after the initial dose, for the Phase 3 study."

Clinical • P1 data • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Lymphoma • Lymphoplasmacytic Lymphoma • Meningococcal Infections • Systemic Lupus Erythematosus • Waldenstrom Macroglobulinemia

VITALIZE: A Study to Test the Efficacy and Safety of Riliprubart Against the Usual Treatment of Intravenous Immunoglobulin (IVIg) in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Preliminary Efficacy and Safety Data from the Phase 2 Trial of Riliprubart (SAR445088), a Humanized Monoclonal Antibody Targeting Complement C1s, in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (AAN 2024) - P2 | "These proof-of-concept results demonstrate a favorable benefit:risk profile of riliprubart, which will be further investigated in Phase 3."

Clinical • P2 data • Fatigue • Infectious Disease • Pain • C1S • NEFL • Plasma NfL

MOBILIZE: A Study to Test the Effects and Safety of Riliprubart in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for Which the Usual Treatments do Not Work (clinicaltrials.gov) - P3 | N=140 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Pain

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks. (PubMed, Immunotargets Ther) - "Despite lack of evidence, cyclophosphamide, rituximab and mycophenolate mofetil are commonly used in circumstances of refractoriness and, more debatably, of perceived overdependence on first-line therapies...A new therapeutic option has appeared with efgartigimod, a neonatal Fc receptor blocker, recently shown to significantly lower relapse rate versus placebo, after withdrawal from previous immunotherapy. Other neonatal Fc receptor blockers, nipocalimab and batoclimab, are under study. The C1 complement-inhibitor SAR445088, acting in the proximal portion of the classical complement system, is currently the subject of a new study in treatment-responsive, refractory and treatment-naïve subjects. Finally, Bruton Tyrosine Kinase inhibitors, which exert anti-B cell effects, may represent another future research avenue. The widening of the therapeutic armamentarium enhances the need for improved evaluation of treatment effects and reliable biomarkers in CIDP."

IO biomarker • Journal • Review • Bone Marrow Transplantation • Immunology • Pain • Transplantation

MOBILIZE: A Study to Test the Effects and Safety of Riliprubart in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for Which the Usual Treatments do Not Work (clinicaltrials.gov) - P3 | N=140 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Pain

VITALIZE: A Study to Test the Efficacy and Safety of Riliprubart Against the Usual Treatment of Intravenous Immunoglobulin (IVIg) in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (clinicaltrials.gov) - P3 | N=160 | Not yet recruiting | Sponsor: Sanofi

New P3 trial • Pain

Proof-of-concept Study for SAR445088 in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: Bioverativ, a Sanofi company | Recruiting ➔ Active, not recruiting

Enrollment closed • Pain

A Phase 2a Study Evaluating BIVV020 in Adults With Persistent/Chronic Immune Thrombocytopenia (ITP) (clinicaltrials.gov) - P2 | N=12 | Completed | Sponsor: Bioverativ, a Sanofi company | Phase classification: P2a ➔ P2

Phase classification • Hematological Disorders • Thrombocytopenia • Thrombocytopenic Purpura

Safety and Tolerability Study in Adults With Cold Agglutinin Disease Previously Treated With SAR445088 or Never Treated With SAR445088 (clinicaltrials.gov) - P1 | N=9 | Active, not recruiting | Sponsor: Bioverativ, a Sanofi company | Trial completion date: Jun 2028 ➔ Jan 2026 | Trial primary completion date: Jun 2028 ➔ Jan 2026

Trial completion date • Trial primary completion date • Anemia • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Immunology