lunsekimig (SAR443765) / Sanofi - LARVOL DELTA

A proof-of-mechanism trial in asthma with lunsekimig, a bispecific nanobody® molecule. (PubMed, Eur Respir J) - "A single dose of lunsekimig was well tolerated, significantly suppressed Type 2 inflammation, and improved lung function in mild-to-moderate asthma."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP

Lunsekimig: Data readout from P2b AIRCULES trial (NCT06102005) for asthma in 2026 (Sanofi) - Q4 & FY 2024 Results: Data readout from P2 trial (NCT06454240) for chronic rhinosinusitis with nasal polyps in 2026

P2 data • P2b data • Asthma • Chronic Rhinosinusitis With Nasal Polyps • Immunology

A Study to Investigate the Efficacy and Safety of Subcutaneous Lunsekimig (SAR443765) Compared With Placebo in Adult Participants With Moderate-to-severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=144 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Study of Lunsekimig (SAR443765) Compared With Placebo in Adults With High-risk Asthma (clinicaltrials.gov) - P2 | N=1000 | Recruiting | Sponsor: Sanofi

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Sanofi Healthcare Gets CDSCO Panel Nod To Study Asthma Drug SAR443765 (Medical Dialogues) - "The drug major Sanofi Healthcare has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation CDSCO to conduct the trial of the pulmonary drug SAR443765(lunsekimig) solution for injection 165 mg/1.1 mL (150 mg/mL). This came after the firm presented phase 2 clinical trial protocol no. LTS17231 Version No. 1 Protocol Date 07-JUN-2024. This is a phase 2, open-label extension study to evaluate the long-term safety and efficacy of lunsekimig in adult participants with moderate-to-severe asthma who have previously completed the parent study. After completion of the parent study, eligible participants will be offered the opportunity to participate in the long-term extension (LTE) study with Lunsekimig."

New P2 trial • Asthma • Immunology

AIRPHRODITE: Long-term Safety and Efficacy Evaluation of Lunsekimig (SAR443765) in Adult Participants With Moderatetosevere Asthma. (clinicaltrials.gov) - P2 | N=467 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

AIRPHRODITE: Long-term Safety and Efficacy Evaluation of Lunsekimig (SAR443765) in Adult Participants With Moderatetosevere Asthma. (clinicaltrials.gov) - P2 | N=467 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

A Proof-of-concept Study of Lunsekimig Compared With Placebo in Adults With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

TSLP AND IL-13 Dual Blockade By Lunsekimig Provides Broader Benefits On Type-2 Inflammation (ERS 2024) - "Indeed, lunsekimig was more potent in inhibiting TARC and eotaxin-3 production than targeting TSLP (tezepelumab) or IL-13 (lebrikizumab) alone in an allergen-stimulated triculture assay. Lunsekimig had significantly lowered plasma human IL­13 and TSLP levels, and inflammation in the PBMC-engrafted immunodeficient mice. Conclusion These results support the hypothesis that a dual-targeting approach to TSLP and IL-13 inhibition may result in synergistic function and support the use of lunsekimig in human asthma clinical trials."

Asthma • Inflammation • Respiratory Diseases • IL13 • TSLP

A Proof-of-concept Study of Lunsekimig Compared With Placebo in Adults With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Sanofi | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Jan 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

A Proof-of-concept Study of Lunsekimig Compared With Placebo in Adults With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Sanofi | Trial completion date: Apr 2027 ➔ Apr 2026

Trial completion date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Lunsekimig: Data readout from P2b AIRCULES trial (NCT06102005) for asthma in H2 2025 (Sanofi) - Q2 2024 Results

P2b data • Asthma • Immunology

A first-in-human, single and multiple dose study of lunsekimig, a novel anti-TSLP/anti-IL-13 NANOBODY® compound, in healthy volunteers. (PubMed, Clin Transl Sci) - "ADA of low titers were detected in four (11.1%) participants who received lunsekimig in the SAD, and seven (43.8%) in the MAD. In conclusion, lunsekimig was well tolerated in healthy participants with a linear PK profile up to single 400 mg IV and SC dose and multiple doses of 100 and 200 mg SC Q2W, with low immunogenicity."

Clinical • Journal • P1 data • Asthma • Immunology • Infectious Disease • Novel Coronavirus Disease • Pain • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP

A Proof-of-concept Study of Lunsekimig Compared With Placebo in Adults With Chronic Rhinosinusitis With Nasal Polyps (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Single-cell RNA Sequencing Analysis of Blood and Nasal Brushing From Asthma Patients Receiving a Single Dose of SAR443765, A Novel, Bispecific Anti-TSLP/Anti-IL-13 Nanobody® Molecule Reveals Significant Impact on Multiple Pathological Immune Cell Populations and Downregulation of CCL26 Expression in Epithelial Cell Subpopulations (ATS 2024) - P1 | "The scRNAseq analysis suggests that a single dose of SAR443765 has specific effects on NB and blood classical/non-classical monocyte populations and can specifically downregulate CCL26 expression in NB epithelial cells suggesting a reduction in inflammatory cell chemotaxis in the lung. 1NANOBODY is a registered trademark by Sanofi. 2Deiteren et al."

Clinical • Immune cell • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • CD8 • IL13 • TSLP

Investigational thymic stromal lymphopoietin inhibitors for the treatment of asthma: a systematic review. (PubMed, Expert Opin Investig Drugs) - "Currently, the only TSLP inhibitor approved for the treatment of severe asthma is the immunoglobulin G (IgG) 2λ anti-TSLP monoclonal antibody (mAb) tezepelumab...Ecleralimab, an inhaled antibody fragment antigen binding, shows promising evidence in enhancing efficacy and reducing systemic adverse events. SAR443765, with its NANOBODY® formulation and bispecific inhibition of TSLP and IL-13, offers improved tissue penetration and efficacy. The mAB TQC2731 exhibits high in vitro bioactivity, and the strength of the mAb UPB-101 is to act against the TSLP receptor...This systematic review highlights the potential of TSLP inhibitors as valuable additions to asthma treatment, even in milder forms of the disease. Future research and cost-reduction efforts are needed to expanding access to these promising therapies."

Journal • Review • Stroma • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CRLF2 • IL13 • TSLP

AIRCULES: Dose Ranging Study of SAR443765 Compared With Placebo-control in Adult Participants With Moderate to Severe Asthma (clinicaltrials.gov) - P2 | N=630 | Recruiting | Sponsor: Sanofi

New P2 trial • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Late Breaking Abstract - Early improvement in asthma small airway dysfunction after one dose of SAR443765, a novel bispecific anti-thymic stromal lymphopoietin/anti-IL-13 nanobody molecule (ERS 2023) - P1 | "A single dose of the novel anti-TSLP/anti-IL-13 biologic nanobody molecule SAR443765 improved lung function and small airway dysfunction in asthma. These effects surpass those reported for monovalent IL-13 or TSLP pathway targeting and suggest potential for superior effects in patients with asthma. Study and medical writing funded by Sanofi 1Deiteren et al."

Late-breaking abstract • Stroma • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Transplantation • IL13 • TSLP

Media Update: New data at ERS showcases Sanofi's scientific leadership in addressing unmet needs across a variety of respiratory conditions (Sanofi Press Release) - "15 abstracts evaluating several Sanofi and collaboration products and investigational treatments will be presented at the 2023 European Respiratory Society (ERS) International Congress from September 9-13 in Milan, Italy....Results from the Dupixent Phase 3 trial (BOREAS)...will be presented as an oral presentation during the New England Journal of Medicine NEJM/ERS journal session and as a late breaking abstract. Additionally, new data from a Phase 3 trial in children aged 6 to 11 years with moderate-to-severe asthma (VOYAGE)....Data from Sanofi’s Phase 1b study of SAR443765 in adults with asthma also demonstrate proof-of-mechanism, the first report of a novel biologic targeting both the thymic stromal lymphopoietin (TSLP) and interleukin-13 (IL-13) pathways."

Clinical data • Late-breaking abstract • P1 data • P3 data • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Respiratory Diseases

Targeting of TSLP and IL-13 by the Novel NANOBODY® Molecule SAR443765 Reduces FeNO in Asthma Following Single Dose Exposure (ATS 2023) - P1 | "Notwithstanding that lung function was normal to near-normal at baseline, rapid numerical improvement was seen for pre-bronchodilator FEV1 in the SAR443765 group as of week 1 that was largely maintained through Day 29.This is the first report of a novel biological targeting both TSLP and IL-13. The rapid and substantial reduction seen in FeNO surpasses that seen in monovalent targeting of either pathway and suggests the potential for superior suppression of airway inflammation and preservation in airway function in asthma."

Asthma • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL5 • TSLP

First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Sanofi | Active, not recruiting ➔ Completed

Trial completion • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP

First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP

First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Sanofi | Trial completion date: Dec 2022 ➔ Apr 2023 | Trial primary completion date: Dec 2022 ➔ Apr 2023

Trial completion date • Trial primary completion date • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP

First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Sanofi | N=72 ➔ 36

Enrollment change • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP

First-in-human Study of SAR443765 in Healthy Participants and in Asthmatic Participants (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Sanofi | Not yet recruiting ➔ Recruiting

Enrollment open • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • TSLP