SAR445399 / Sanofi, MAB Discovery - LARVOL DELTA

Sanofi suspends chronic lung disease phase 2 study, tied to ‘strategic business reasons’ (FierceBiotech) - "The decision to pause the trial was made 'as part of a company-wide portfolio review for strategic business reasons,' and not due to safety concerns, a Sanofi spokesperson told Fierce."

Trial suspension • Immunology • Non‐Cystic Fibrosis Bronchiectasis

A Study to Access Activity and Safety With SAR445399 Compared With Placebo in Participants Aged 18 to 80 Years of Age With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=70 | Suspended | Sponsor: Sanofi | Trial completion date: Aug 2028 ➔ May 2029 | Recruiting ➔ Suspended

Trial completion date • Trial suspension • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

PDY19372: A Study to Access Activity and Safety with SAR445399 Compared with Placebo in Participants Aged 18 to 80 Years of Age with Non-Cystic Fibrosis Bronchiectasis (clinicaltrialsregister.eu) - P1/2 | N=25 | Not yet recruiting | Sponsor: Sanofi-Aventis Recherche & Developpement

New P1/2 trial • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Access Activity and Safety With SAR445399 Compared With Placebo in Participants Aged 18 to 80 Years of Age With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Access Activity and Safety With SAR445399 Compared With Placebo in Participants Aged 18 to 80 Years of Age With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P2 | N=70 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Multi-Omics analysis of SAR445399, an IL-1R3 antagonist: anti-inflammatory effects in skin challenges from Phase 1 study (AAD 2026) - "Background: In an innovative proof-of-mechanism study, we evaluated SAR445399, a first-in-class anti-IL-1R3 antibody, in healthy subjects using lipopolysaccharide (LPS) and imiquimod (IMQ) as challenge models, with spesolimab and canakinumab as comparators. SAR445399 effectively modulates key inflammatory mediators and pathways at skin level after LPS and IMQ challenge as demonstrated by comprehensive proteomic and transcriptomic profiling. This observed effect strongly supports the rationale for further clinical development in dermatological conditions where IL-1 and IL-36 signaling play crucial pathogenic roles."

P1 data • Dermatitis • Inflammation • IL17A • IL17C • IL1RAP • IL6

CLAROS: A Study to Investigate Efficacy and Safety With SAR445399 in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=144 | Recruiting | Sponsor: Sanofi | N=74 ➔ 144

Enrollment change • Trial initiation date • Dermatology • Hidradenitis Suppurativa • Immunology

IL-1R3 Antagonism With Sar445399 in Skin Challenge Model: Translational Evidence for Chronic Respiratory Diseases (ATS 2026) - No abstract available

Respiratory Diseases • IL1RAP

CLAROS: A Study to Investigate Efficacy and Safety With SAR445399 in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=144 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Hidradenitis Suppurativa • Immunology

CLAROS: A Study to Investigate Efficacy and Safety With SAR445399 in Adult Participants With Moderate to Severe Hidradenitis Suppurativa (clinicaltrials.gov) - P2 | N=144 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Dermatology • Hidradenitis Suppurativa • Immunology

The novel, first-in-class IL-1R3 Antagonist SAR445399 Reduces Skin Inflammation in an Innovative Proof-of-Mechanism Study with Dual Immune Challenge Models and Comparator Drugs (EADV 2025) - "This study was designed to evaluate the effect of SAR445399 on dermal inflammation induced by imiquimod (IMQ) and lipopolysaccharide (LPS) which trigger a local skin reaction via IL-36 and IL-1 pathways. In this innovative study SAR445399 demonstrated significant inhibition of skin inflammation after LPS and IMQ challenges via the IL-1 and IL-36 pathways. Canakinumab also inhibited LPS and IMQ induced skin inflammation while spesolimab was effective in the IMQ model only. Results are in line with scientific literature describing IL-1 contribution to the LPS and IL-1/ IL-36 contribution to the IMQ driven skin inflammation."

Dermatitis • Dermatology • Inflammation • IFNG • IL12A • IL17C • IL1B • IL1RAP • IL33 • IL6

SAR445399 – an anti-IL-1R3 monoclonal antibody that blocks IL-1, IL-33 and IL-36 cytokine pathways for dermatologic diseases (ISDS 2023) - "Multiple therapies targeting individual members of the IL-1 family have only shown low to moderate efficacy in dermatologic disorders such as: αIL-36γ (Spesolimab) in AD, HS and PPP, αIL-33 (Itepekimab) in AD and IL-1R antagonist (Anakinra) or αIL-1R (MEDI-8968) in HS. Furthermore, an anti-murine surrogate of SAR445399 alleviates disease and inflammation in an Imiquimod-induced skin inflammation model with superior efficacy than IL-1 blockade alone. In summary, SAR445399 is a broad IL-1 pathway drug hitting 3 birds with 1 stone and is uniquely positioned to potentially raising the efficacy ceiling where a single agent therapy may not be fully efficacious in dermatology or other immunology areas."

Atopic Dermatitis • Dermatitis • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • Psoriasis • IL1B • IL1RAP • IL33