CBP-201 is a human monoclonal antibody targeting IL-4Rα, which we have observed to have dose-dependent and differentiated pharmacokinetics and pharmacodynamics in an early clinical trial.
As an inhibitor of IL-4Rα, CBP-201 blocks inflammatory signaling by both IL-4 and IL-13. CBP-201 binds to a region of IL-4Rα that is distinct from that bound by dupilumab (an antibody that targets IL-4Rα and is marketed as Dupixent®). Our clinical development program is focused on differentiating CBP-201 in three areas, with the potential to show rapid onset and sustained clinical outcomes with a convenient dosing frequency.
We have initiated a Phase 2b trial of CBP-201 in patients with moderate-to-severe atopic dermatitis (AD), and plan to initiate additional trials in asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) in 2021.
Atopic dermatitis (Phase 2)
Atopic dermatitis (AD), which has an estimated lifetime prevalence of up to 20% and is increasing globally, is the most commonly diagnosed chronic inflammatory skin disorder.1 It is characterized by skin barrier disruption and immune dysregulation. It is estimated that 26.1 million people in the United States have AD2, of which 6.6 million have moderate-to-severe disease.3 It is estimated that over 58% of adults with moderate-to-severe AD have disease which physicians consider to be inadequately controlled by approved therapeutic modalities, including topical anti-inflammatory agents and systemic agents.4
Type 2 inflammatory asthma (Phase 2)
Type 2 inflammation, which occurs in more than 80% of children and the majority of adults with asthma,5 is an important molecular mechanism that gives rise to asthma symptoms.5 Type 2 inflammation is mediated by type 2 helper T-cells (TH2), which secrete inflammatory cytokines including IL-3, IL-4, L-5, IL-9 and IL-13.5
While corticosteroids have been a pillar of therapy for patients with type 2 inflammatory asthma, they are associated with multiple local and systemic side effects.5 Novel therapies that can inhibit aberrant TH2 activity with greater specificity will be critical for improving the care and outcomes of patients with type 2 inflammatory asthma.5
Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) (Phase 2 expected to commence in 2021)
Chronic rhinosinusitis (CRS), which is characterized by chronic inflammation of the nasal mucosa and paranasal sinuses, is a common condition with an estimated prevalence of 8-11%.6 Approximately 25-30% of individuals with CRS develop nasal polyps, which are growths that occur in the nasal passages and sinuses and are frequently associated with asthma, allergic rhinitis and chronic rhinosinusitis.7 As nasal polyps increase in size and/or number, they can interfere with normal breathing and may also lead to a loss of sense of smell.7 In some cases, nasal polyps may need to be removed surgically.7 Patients with CRS with nasal polyps (CRSwNP) have significant morbidity and decreased quality of life.7 Despite the availability of an injectable biologic for nasal polyps due to chronic rhinosinusitis, many patients continue to have unmet medical need.7
Mechanism of Action
CBP-201 blocks IL-4Rα, a common subunit for IL-4Rα and IL-13 receptors and a validated target for an FDA-approved therapy (dupilumab). Inhibition of IL-4 and IL-13 activity is important because the two cytokines have extensive overlapping functions. Preclinical and clinical data demonstrate that dual inhibition of IL-4 and IL-13 dual is required to achieve desired efficacy in Th2-mediated diseases. CBP-201 binds to IL-4Rα in a manner that prevents the receptor from interacting with other receptor subunits that are required for activation of the signaling pathways that ultimately give rise to Th2-mediated diseases, including atopic dermatitis, asthma and nasal polyps.
Phase 1b Clinical Data in Patients with Moderate-to-Severe Atopic Dermatitis
In a Phase 1b clinical study of CBP-201 in adult patients with moderate-to-severe AD, we observed that multiple doses of CBP-201 were well tolerated. At week four, 88% and 100% of patients receiving CBP-201 150 mg (n=8) or 300 mg (n=7), respectively, achieved a 50% reduction in the Eczema Area and Severity Index score, or EASI-50, and 50.0% and 42.9% and of patients receiving CBP-201 150 mg or 300 mg, respectively, achieved clear/almost clear skin (Investigator Global Assessment 0,1). Additionally, skin lesion improvements were rapid, as evidenced as early as Week 1 after dosing, and were correlated with a rapid reduction in pruritus intensity and frequency. Dermatology Quality of Life Index scores showed improvements at Week 1, and these early and rapid improvement continued to increase through Week 4.
Current Development Status
A Phase 2b dose ranging study with CBP-201 is ongoing to assess its efficacy, safety, pharmacokinetics and pharmacodynamics in patients with moderate-to-severe AD, as well as the potential for dosing every four weeks (NCT04444752).
Posters & Publications
A randomized, double-blind, placebo-controlled, multiple ascending dose study of the safety, pharmacokinetics and preliminary efficacy of CBP-201 in adult patients with moderate to severe atopic dermatitis (CPB-201AU002)
Presented at the the 29th European Academy of Dermatology and Venereology Congress (EADV), October 29, 2020
- Weidninger S, Beck LA, Bieber T, et al. Atopic dermatitis. Nature Reviews Disease Primers. 2018;4:1
- National Eczema Association. Atopic Dermatitis: What is atopic dermatitis? Available at: https://nationaleczema.org/eczema/types-of-eczema/atopic-dermatitis/
- Asthma and Allergy Association of America. Atopic dermatitis in America: Study overview. Available at: https://www.aafa.org/media/2209/Atopic-Dermatitis-in-America-Study-Overview.pdf
- 2014 Adelphi US AD Disease Specific Programme
- Holgate ST, Wenzel S, Postma DS, et al. Asthma. Nature Reviews Disease Primers. 2015;1:15025.
- Yang X, Xu Y, Jin J, et al. Chronic Rhinosinusitis is Associated with Higher Prevalence and Severity of Bronchiectasis in Patients with COPD. International Journal of Chronic Obstructive Pulmonary Diseases. 2017;12:655-662. doi: 10.2147/COPD.S124248.
- Stevens WW, Schleimer RP and Kern RC. Chronics rhinosinusitis with nasal polyps. Journal of Allergy Clinical Immunology