[Translation] A single-center, randomized, double-blind, placebo-controlled Phase Ia clinical study to evaluate the tolerability, safety, immunogenicity and pharmacokinetics of LQ036 via oral inhalation in healthy Chinese subjects

主要目的：评估LQ036在中国健康受试者中单次及多次给药的耐受性和安全性，为后续临床试验提供依据。次要目的： (1) 评估LQ036在中国健康受试者中单次及多次给药的药代动力学特征； (2) 评估LQ036在中国健康受试者中单次及多次给药的药效动力学特征； (3) 评估LQ036在中国健康受试者中单次及多次给药的免疫原性。

[Translation]

Primary objectives: To evaluate the tolerability and safety of LQ036 after single and multiple administrations in healthy Chinese subjects, and to provide a basis for subsequent clinical trials. Secondary objectives: (1) To evaluate the pharmacokinetic characteristics of LQ036 after single and multiple administrations in healthy Chinese subjects; (2) To evaluate the pharmacodynamic characteristics of LQ036 after single and multiple administrations in healthy Chinese subjects; (3) To evaluate the immunogenicity of LQ036 after single and multiple administrations in healthy Chinese subjects.

Start Date27 Nov 2022

Sponsor / Collaborator

Shanghai Novamab Biopharmaceuticals Co., Ltd.

ChiCTR2200063120 / SuspendedPhase 1IIT

A single-center, randomized, double-blind, placebo-controlled phase Ia clinical trial to evaluate the tolerability, safety, immunogenicity and pharmacokinetics of transoral inhalation of nebulized LQ036 in healthy Chinese subjects

Start Date01 Sep 2022

Sponsor / Collaborator

The Second Affiliated Hospital of Anhui Medical University

NCT04993443 / TerminatedPhase 1

A Single and Multiple-dose Escalation First-in-Human Study Evaluating the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of LQ036 Administered Via Inhalation and IV Infusion in Healthy Subjects and Patients With Mild Asthma.

This is Phase I first-in-human trial evaluating the safety, tolerability, immunogenicity, and pharmacogenomics of LQ036 via inhalation and IV infusion.
The study will be divided into 4 parts: Single Ascending Dose, Multiple Ascending Dose, and Intra Venous with a target of 88 healthy volunteers and 30 patients with mild Asthma.

Start Date06 Sep 2021

Sponsor / Collaborator

Syneos Health, Inc.

[+1]

100 Clinical Results associated with Recombinant anti-IL-4Rα nanobody(Shanghai Novamab Biopharmaceuticals)

100 Translational Medicine associated with Recombinant anti-IL-4Rα nanobody(Shanghai Novamab Biopharmaceuticals)

100 Patents (Medical) associated with Recombinant anti-IL-4Rα nanobody(Shanghai Novamab Biopharmaceuticals)

Literatures (Medical) associated with Recombinant anti-IL-4Rα nanobody(Shanghai Novamab Biopharmaceuticals)

01 Oct 2024·Journal of Allergy and Clinical Immunology

A novel inhalable nanobody targeting IL-4Rα for the treatment of asthma

Article

Author: Wan, Yakun ; Li, Xiaofei ; Chen, Zhihong ; Qiao, Peng ; Li, Guanghui ; Ding, Yu ; Sun, Baihe ; Gu, Huaiyu ; Gai, Junwei ; Deng, Zhenzhen ; Zhu, Min ; Huang, Jing ; Zhang, Lei ; Ma, Linlin ; Li, Yanfei ; Zhong, Peiyu ; Yin, Yong

BACKGROUNDInhalable biologics represent a promising approach to improve the efficacy and safety of asthma treatment. Although several mAbs targeting IL-4 receptor α chain (IL-4Rα) have been approved or are undergoing clinical trials, the development of inhalable mAbs targeting IL-4Rα presents significant challenges.OBJECTIVECapitalizing on the distinctive advantages of nanobodies (Nbs) in maintaining efficacy during storage and administration, we sought to develop a novel inhalable IL-4Rα Nb for effectively treating asthma.METHODSThree IL-4Rα immunized Nb libraries were used to generate specific and functional IL-4Rα Nbs. LQ036, a bivalent Nb comprising 2 HuNb103 units, was constructed with a high affinity and specificity for human IL-4Rα. The efficacy, pharmacokinetics, and safety of inhaled LQ036 were evaluated in B-hIL4/hIL4RA humanized mice.RESULTSLQ036 inhibited secreted embryonic alkaline phosphatase reporter activity, inhibited TF-1 cell proliferation, and suppressed phosphorylated signal transducer and activator of transduction 6 in T cells from patients with asthma. Crystal structure analysis revealed a binding region similar to dupilumab but with higher affinity, leading to better efficacy in blocking the signaling pathway. HuNb103 competed with IL-4 and IL-13 for IL-4Rα binding. Additionally, LQ036 significantly inhibited ovalbumin-specific IgE levels in serum, CCL17 levels in bronchoalveolar lavage fluid, bronchial mucous cell hyperplasia, and airway goblet cell hyperplasia in B-hIL4/hIL4RA humanized mice. Inhaled LQ036 exhibited favorable pharmacokinetics, safety, and tissue distribution, with higher concentrations observed in the lungs and bronchi.CONCLUSIONSThese findings from preclinical studies establish the safety and efficacy of inhaled LQ036, underscoring its potential as a pioneering inhalable biologic therapy for asthma.

01 Jan 2024·Pediatric Dermatology

Severe eczema in Wiskott–Aldrich syndrome‐related disorder successfully treated with dupilumab

Article

Author: Miller, Holly K ; Dupuy, Elizabeth ; Sacco, Keith ; Alzahrani, Fatmah

AbstractTreatment of severe eczema in patients with primary immunodeficiencies can be particularly challenging as there are no guidelines with regards to these conditions. Dupilumab is an interleukin (IL)‐4Rα antagonist that inhibits both IL‐4 and IL‐13 and is approved for the treatment of atopic dermatitis in pediatric patients. In this report, we describe a patient with a case of severe eczema in the context of Wiskott–Aldrich syndrome‐related disorder, who was successfully treated with dupilumab.

01 Jul 2022·Allergy

JAK1/2 inhibitor but not IL‐4 receptor alpha antibody suppresses allergen‐mediated activation of human basophils in vitro

Letter

Author: Yu, Chunfeng ; Benfadal, Said ; Novak, Natalija ; Wenzel, Jörg ; Peng, Wenming ; Oldenburg, Johannes

The present study aimed to evaluate the suppressive function of dupilumab and baricitinib on FcεRI-mediated human basophil activation in vitro.In line with previous reports, significant basophil infiltration was detected in the lesional skin of AD patients but not in the skin of healthy donors.Results from flow cytometric intracellular phosphoprotein staining demonstrated that the JAK1/2 inhibitor, but not dupilumab, specifically suppressed the activation of STAT3, an essential mol. in the JAK-STAT pathway.Western blot anal. confirmed that the JAK1/2 inhibitor suppressed the activation of STAT3 as well as FcεRI-mediated activation of Syk and PKC, indicating the JAK1/2 inhibitor suppresses basophil activation and degranulation via FcεRI-mediated signaling.Our study confirmed skin infiltration of basophils in the lesional skin of AD patients.Our results suggested that baricitinib may exert its anti-pruritic function by suppressing the activation of skin-infiltrating basophils in AD patients.Although the IL-4Rα antagonist did not display its suppressive function on basophil activation in our in vitro experiments, it is still possible that the IL-4Rα antagonistic biologics exert an indirect suppressive function on basophils through suppression of the activation of Th2 cells in vivo.The suppressive function of the JAK1/2 inhibitor baricitinib on activated basophils demonstrated here in vitro might be responsible for the fast and strong effect of.JAK inhibitors including baricitinib on allergic skin inflammation and skin lesions in AD patients observed in clin. studies.

100 Deals associated with Recombinant anti-IL-4Rα nanobody(Shanghai Novamab Biopharmaceuticals)

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Indication	Highest Phase	Country/Location	Organization	Date
Asthma	Phase 2	CN	Shanghai Novamab Biopharmaceuticals Co., Ltd.	04 Feb 2024
Pulmonary Disease, Chronic Obstructive	IND Approval	CN	Shanghai Novamab Biopharmaceuticals Co., Ltd.	15 Sep 2023

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