CBP-201 is a human monoclonal antibody targeting IL-4Rα, which we have observed to have dose-dependent and differentiated pharmacokinetics and pharmacodynamics in early clinical trials.
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 improvements in clinical outcomes with a convenient dosing frequency.
Target Indications
Atopic dermatitis (Pivotal China trial)
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 that 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)
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 and asthma.
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.
Global Phase 2b Clinical Data in Adult Patients with Moderate-to-Severe Atopic Dermatitis
Data from a global Phase 2b clinical trial in adult patients with moderate-to-severe AD found that all three doses of CBP-201 evaluated (300mg Q2W, 150mg Q2W or 300mg Q4W) met the primary endpoint of eczema area and severity index (EASI) percent reduction from baseline at Week 16 and were statistically superior to placebo. For EASI secondary endpoints, all three CBP-201 arms showed statistically significant improvements in the proportion of patients achieving at least a 50% or 75% reduction in EASI score from baseline at Week 16, compared with placebo (EASI-50 or EASI-75, respectively).The Phase 2b study also achieved key secondary endpoints of Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and a reduction of >2 points from baseline at Week 16, and change from baseline to Week 16 in weekly average Peak Pruritus-Numerical Rating Scale (PP-NRS).
CBP-201 was also observed to have a favorable safety profile, with a similar incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs leading to study drug discontinuation reported for CBP-201 treatment and placebo groups. Finally, there were a low reported incidence of injection site reactions (1.8%), conjunctivitis (3.5%), and herpes infections (0.6%) in patients receiving CBP-201.
Based on the results of the global Phase 2b trial, we are confident about the potential for a highly competitive efficacy and safety profile for CBP-201 coupled with a more convenient and differentiated Q4W dosing schedule.
Current Development Status
Based on the positive data from the completed global Phase 2b trial, we will look for potential global and regional partners who will further Connect Biopharma’s goal of delivering a differentiated therapeutic program with improved efficacy and dosing convenience.
Pivotal China-only AD Trial: Reported interim Stage 1 results, currently in Stage 2 (maintenance)
CBP-201 is also in an ongoing trial in moderate-to-severe AD in China in which it reported positive topline results meeting all primary and secondary endpoints.
Stage one of the China trial compared a 2-week dosing arm (Q2W) with placebo. Stage 2, which is currently ongoing, includes 2-week and 4-week (Q4W) dosing arms. We expect this second stage will provide more insight into the potential for an extended Q4W dosing regimen, which would substantially differentiate CBP-201 from existing treatments, which are Q2W.
The China trial is the largest trial, to date, of this class of drug in China (n=255). China’s Center for Drug Evaluation (CDE) has indicated that depending on the results, it could review CBP-201 for approval based on this trial. Accordingly, there is the potential for Connect to file an NDA with the Chinese CDE in 2024 and receive potential NDA approval in China as early as 2025.
Ongoing Phase 2 trial for CBP-201 for the treatment of patients with severe asthma with type 2 inflammation
Connect’s Phase 2 trial of CBP-201 to treat patients with severe asthma with type 2 inflammation is anticipated to complete full enrollment in the first half of 2023 and targets reporting the Phase 2 top-line result of CBP-201 in asthma in the second half of 2023.
Posters & Publications
CBP-201, a novel and differentiated IL-4Rα targeting antibody being evaluated in Th2 inflammatory diseases
SID Annual Meeting, May 18-21, 2022
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
Efficacy and Safety of CBP-201 in Adults with Moderate-to-Severe Atopic Dermatitis (AD): A Phase 2b, Randomized, Double-blind, Placebo-controlled Trial (CBP-201-WW001)
Presented at the Maui Derm Conference, January 24, 2022
The Effect of Baseline Disease Characteristics on Efficacy Outcomes: Results from a Phase 2b, Randomized, Double-blind, Placebo-controlled Trial of CBP-201 in Adults with Moderate-to-Severe Atopic Dermatitis (AD)
Presented at the Maui Derm Conference, January 24, 2022
Efficacy and Safety of CBP-201 in Adults with Moderate-to-Severe Atopic Dermatitis (AD): A Phase 2b, Randomized, Double-blind, Placebo-controlled Trial (CBP-201-WW001)
Presented at the Maui Derm Conference, January 24, 2022
The Effect of Baseline Disease Characteristics on Efficacy Outcomes: Results from a Phase 2b, Randomized, Double-blind, Placebo-controlled Trial (CBP-201-WW001)
Presented at the Maui Derm Conference, January 24, 2022
- 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