Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multi-system, inflammatory disorder and is classified under the group of ANCA-associated vasculitides. As a leading-edge innovator in rare cardiovascular disease therapy research, Protheragen provides one-stop comprehensive drug discovery and development services to support the development of new therapeutics for individuals with rare cardiovascular diseases such as EGPA.

Introduction to Eosinophilic Granulomatosis with Polyangiitis (EGPA)

EGPA, formerly known as Churg-Strauss syndrome, manifests as late-onset asthma, eosinophilia, and small-to-medium-sized vessel vasculitis. The cardiac involvement in EGPA is characterized by the heterogeneity of presentation despite its high mortality. The annual prevalence and incidence of EGPA are 0.7/1,000,000 to 2.4/1,000,000 persons and 10.7/1,000,000 to 17.8/1,000,000 persons, respectively.

These genetic disparities between ANCA-positive and ANCA-negative EGPA.

Fig.1 Through different genetics, different pathophysiology occurs. (Watanabe, R., and Hashimoto, M., 2023)

Pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA)

T-cell activation is pivotal to the pathogenesis and both an antigen-driven and allergen-driven mechanism has been suggested given the human leucocyte antigen (HLA) expression found in EGPA. Increased T-helper (TH) cell activation in active EGPA could be triggered by an unknown antigen in the aetiopathogenesis of the disease. Three conjoined inflammatory pathways have been activated in EGPA: endothelial eotaxin-3, TH2 at drive, and B cells, resulting in humoral response activation.

ANCA-positive and ANCA-negative EGPA present as distinct phenotypes.

Fig.2 Expressions of ANCA-positive and ANCA-negative EGPA vary. (Watanabe, R., and Hashimoto, M., 2023)

Therapeutics Development for Eosinophilic Granulomatosis with Polyangiitis (EGPA)

Drug Name	Mechanism of Action	Targets	NCT Number	Research Phase
Benralizumab	Binding to the eosinophil surface interleukin-5 receptor alpha (IL-5Rα) and inducing their targeted depletion and a decrease in eosinophil-related inflammation.	IL-5Rα	NCT06512883	Phase III
Tezepelumab	TSLP inhibition to decrease eosinophil-mediated inflammation and alteration of the immune responses implicated in the disease.	TSLP	NCT06230354	Phase II
NS-229	A selective JAK1 inhibitor, which inhibits the over-activation of eosinophils by inhibiting JAK1-mediated signaling pathways.	JAK1	NCT06046222	Phase II
SHR-1703	A novel humanized IgG1 monoclonal antibody of super high affinity to IL-5 with extended half-life in development for the therapy of eosinophilic diseases.	IL-5	NCT05979051	Phase II/III

Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a therapy plan recommendation. For guidance on therapy options, please visit a regular hospital.

Our Services

Providing an integrated platform for end-to-end drug discovery and development, our service offerings include next-generation diagnostics, therapeutics, and disease modeling. This allows us to work collaboratively to move between concept and application candidates faster, and more effectively.

Therapeutic Development Services

Diverse Platforms

Animal Model Development for EGPA

Animal models are indispensable tools for investigating the complex pathophysiology of EGPA, as they provide the means to investigate disease mechanisms, discover novel therapeutic targets, and test the effectiveness and safety of novel therapeutics before they are introduced into human trials. With the support of advanced techniques and our talented scientist team, we have developed tailored EGPA animal model services to meet the unique needs of our customers.

Induced Animal Models

Animals can be sensitized to allergens such as ovalbumin (OVA) or house dust mite extract to elicit eosinophilic inflammation.

OVA-induced model
Other models

Genetically Engineered Models

IL-5 transgenic animals (animals engineered to express high levels of IL-5) display severe eosinophilia.

IL-5 Transgenic model
Other models

By harnessing cutting-edge technologies and an outstanding team of experienced professionals, Protheragen's preclinical capabilities include comprehensive pharmacokinetic studies and thorough safety evaluation. Focused on accuracy and reliability, we supply the critical information necessary for making practical and effective decisions and designing and developing successful drugs and therapeutics. Please get in touch with us if you would like to know how we can customize our services to support your research.

References

Watanabe, Ryu, and Motomu Hashimoto. "Eosinophilic Granulomatosis with Polyangiitis: Latest Findings and Updated Treatment Recommendations." Journal of clinical medicine 12.18 (2023): 5996.
White, Jpe, and S Dubey. "Eosinophilic granulomatosis with polyangiitis: A review." Autoimmunity reviews 22.1 (2023): 103219.

For research use only, not for clinical use.