Innovent Announces First Participant Dosed in a Phase I Study of IBI3002 (an anti-IL-4Rα/TSLP bispecific antibody) in Australia

ROCKVILLE, Md. and SUZHOU, China, March 1, 2024 /PRNewswire/ -- Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune, ophthalmology and other major diseases, announces that the first participant has been dosed in Australia in a first-in-human (FIH) phase 1 clinical trial of IBI3002, a global first-in-class bispecific antibody targeting Interleukin 4 receptor α (IL-4Rα) and thymic stromal lymphopoietin (TSLP).

This FIH study (NCT06213844) is a randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) (only in participants with asthma) of IBI3002 in healthy participants and participants with mild to moderate asthma, and to support further global clinical development of IBI3002.

IBI3002 is a humanized bispecific antibody targeting cell surface IL-4Rα and the alarmin cytokine TSLP, discovered and developed by Innovent for the treatment of inflammatory diseases, including asthma. IL-4 receptors mediate the IL-4 signaling (both type 1 and type 2) and the IL-13 signaling (type 2). Both cytokine signaling pathways play key roles in the pathophysiology of type 2 (T2) inflammatory disorders¹. TSLP is an epithelial cell-derived alarmin cytokine and triggers both T2 and non-T2 inflammation in asthma².

IBI3002 has high-efficient dual-blocking function on both IL-4Rα and TSLP. In-vitro assays have shown superiority over the marketed monoclonal antibodies to respective target. By targeting both IL-4Rα and TSLP, IBI3002 is hypothesized to have potential effect in suppressing T2 and non-T2 inflammation. The potential synergistic effect in suppressing T2 inflammation is believed to be the basis of its superior efficacy in the treatment of T2 inflammatory disorders.

Dr. Lei Qian, Vice President of Clinical Development at Innovent, stated, "In the last few decades, knowledge about both pathophysiological mechanisms, clinical phenotypes and therapeutic options for asthma have significantly increased. In particular, the introduction of biologics for severe asthma paved the way to a true revolution in the field of asthma management, by potentially allowing a precision medicine approach. Targeting specific steps of the immune-inflammatory cascade through highly selective drugs represents a true revolution in the field of severe asthma management, and brings with it the potential of achieving optimal disease control in different severe asthma inflammatory phenotypes. We are looking forward to the development of this molecule in asthma and other inflammatory diseases."

About Asthma

Asthma is a heterogeneous disease driven by multiple immune cells, cytokines and inflammatory mediators, affecting all age groups. Characterized by variable symptoms of wheeze, shortness of breath, cough, and chest tightness, asthma is associated with chronic airway inflammation, reversible airflow limitation, and airway hyperresponsiveness³. According to the 2015 Global Burden of Disease (GBD) study, about 358 million people are suffering from asthma⁴. Asthma can be broadly classified as eosinophilic or non-eosinophilic on the basis of airway or peripheral blood cellular profiles. Eosinophilic inflammation is driven predominantly by T2 inflammation, including T-helper cells type 2 and group 2 innate lymphoid cells⁵. Compared with eosinophilic asthma, non-eosinophilic asthma is poorly understood⁶. Up to 10% of adults and 2.5% of children with asthma have severe asthma⁷. Patients with severe asthma have persistent symptoms or frequent exacerbations that require repetitive systemic glucocorticoid bursts or maintenance, despite adequate treatment with high-dose inhaled treatments⁸. In these patients, add-on treatment, which may include biologic therapies, is needed to reduce the disease burden^2,3.

About IBI3002

IBI3002 is a global first-in-class bispecific antibody targeting cell surface IL-4Rα and the alarmin cytokine TSLP. It has high-efficient dual-blocking function on both IL-4Rα and TSLP. In-vitro assays have shown superiority over the marketed monoclonal antibodies to respective targets. By simultaneously targeting IL-4Rα and TSLP, IBI3002 has the potential of treating several inflammatory disorders, including asthma.

IL-4 is a central mediator of type 2 lymphocyte cell differentiation; it induces the production of type 2 associated cytokines such as IL-5, IL-9, IL-13, and/or type 2 related chemokines as thymus and activation-regulated chemokine (TARC/CCL17) and eotaxins-3. IL-4 involved in B cells regulated isotype class switching to produce serum IgE, and the eosinophils recruitment through IL-5 releasement. Although IL-13 displays some redundancies in these pro-inflammatory processes, it has additional roles in mediating goblet cell hyperplasia, mucus production, smooth muscle contractility, and airway hyperresponsiveness. Together, IL-4 and IL-13 play critical roles in T2 inflammation¹.

TSLP is an epithelial cell-derived alarmin cytokine that occupies an upstream position in the T2 inflammation induction and Th2 cells differentiation and maturation via IL-4, IL-5 and IL-13 production. TSLP is also believed to be a trigger of non-T2 inflammation in asthma ².

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable illnesses. Its pioneering therapies to treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 4 assets in Phase III or pivotal clinical trials and 20 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).

Forward-looking statement

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent Biologics ("Innovent"), are intended to identify certain of such forward-looking statements. The Company does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of the Company with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond the Company's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialise or turn out to be incorrect.

References: 

1.        Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production[J]. Cytokine, 2015, 75(1): 14-24.

2.        Brusselle G G, Koppelman G H. Biologic therapies for severe asthma[J]. New England Journal of Medicine, 2022, 386(2): 157-171.

3.        Global Initiative for Asthma. 2023 GINA Report, Global Strategy for Asthma Management and Prevention. 2023.

4.        GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet Respir Med. 2017 Oct;5(10 ):e30]. Lancet Respir Med. 2017;5(9):691-706.

5.        Gans MD, Gavrilova T. Understanding the immunology of asthma: Pathophysiology, biomarkers, and treatments for asthma endotypes. Paediatr Respir Rev. 2020;36:118-127.

6.        Israel E, Reddel H K. Severe and difficult-to-treat asthma in adults[J]. New England Journal of Medicine, 2017, 377(10): 965-976.

7.        Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol 2019; 123(6): 564-572.e3.

8.        Caminati M, Vaia R, Furci F, Guarnieri G, Senna G. Uncontrolled Asthma: Unmet Needs in the Management of Patients. J Asthma Allergy. 2021;14:457-466.