Connect Biopharma Announces Positive Phase 1b Clinical Results for CBP-201 in Moderate-to-Severe Atopic Dermatitis

Data show that CBP-201 demonstrates superior efficacy and a more rapid onset of action after 4 weeks of treatment compared with the current standard biologic therapy (dupilumab) for moderate-to-severe atopic dermatitis.

On Day 29, among patients with moderate-to-severe atopic dermatitis treated with CBP-201, 42.9% (300 mg dose group) and 50.0% (150 mg dose group) achieved an Investigator’s Global Assessment (IGA) score of 0 or 1, indicating complete or almost complete clearance of skin symptoms. This endpoint, which is required for FDA approval, was significantly higher than the 12.5% observed in the placebo group.

Connect Biopharma is a biopharmaceutical company focused on the research and development of novel therapeutics for autoimmune diseases, with clinical-stage products in its pipeline. On January 8, 2020, the company announced positive data from its Phase 1b clinical study of CBP-201, a novel IL-4Rα antibody, in patients with moderate-to-severe atopic dermatitis conducted in Australia and New Zealand. The data demonstrated that CBP-201 achieved superior efficacy after four weeks of treatment compared to existing data for standard biologic therapies for atopic dermatitis, with a favorable safety profile. The company expects to initiate a global Phase 2b clinical trial of CBP-201 for moderate-to-severe atopic dermatitis in the first quarter of 2020. This trial will involve dozens of clinical centers across the United States and Europe and will enroll more than 200 patients.

Atopic dermatitis is a chronic inflammatory skin disease characterized by eczematous lesions, pruritus, xerosis, and sleep disturbances, imposing multiple negative impacts on patients’ quality of life. It is a common condition, with an estimated prevalence of 10–15% in children and 2–4% in adults. Approximately 30% of patients with atopic dermatitis have moderate-to-severe disease. Currently, there remains a significant unmet medical need among patients with moderate-to-severe atopic dermatitis whose condition is inadequately controlled with topical corticosteroid therapy.

Dr. Mike Royal, Chief Medical Officer at Connect Biopharma, stated, “Although CBP-201 is still in the early stages of clinical development, positive data from the Phase 1b clinical trial indicate that CBP-201 can bring about comprehensive improvement in patients with atopic dermatitis after just four weeks of treatment. Among patients receiving CBP-201, 42.9% (300 mg dose group) and 50.0% (150 mg dose group) of subjects achieved complete or almost complete clearance of skin symptoms after four weeks. In contrast, current standard biologic therapies for atopic dermatitis show a placebo-adjusted improvement rate of only 22–28% after up to 16 weeks of treatment. The clinical efficacy of CBP-201 is highly encouraging! We will obtain more data from the Phase 2b clinical study to further explore the significant role of CBP-201 in treating moderate-to-severe atopic dermatitis.”

Dr. Zheng Wei, Co-founder and CEO of Connect Biopharma, stated, “We are very pleased to see that CBP-201 demonstrated excellent tolerability and rapid onset of action after four weeks of treatment in patients with moderate-to-severe atopic dermatitis. These data further support the potential of CBP-201 as a best-in-class novel drug. In addition, while current standard biologic therapies require dosing every two weeks, CBP-201 has the potential to enable a more favorable dosing regimen of once every four weeks, which will contribute to its clinical and commercial success. We look forward to further validating the positive results from the Phase 1b trial in the Phase 2b clinical study, which was initiated in the first quarter of 2020.”

CBP-201 Treatment Rapidly Improves Skin Lesions in 29 Days! This is based on the assessment criteria of changes from baseline in Investigator’s Global Assessment (IGA) and Eczema Area and Severity Index (EASI).

● 42.9% (300 mg dose group) and 50.0% (150 mg dose group) of patients achieved an Investigator’s Global Assessment (IGA) score of 0 or 1, indicating complete or almost complete clearance of skin symptoms, which is the primary endpoint required for FDA approval; these rates were significantly higher than the 12.5% observed in the placebo group.

●100% (300 mg dose group) and 87.5% (150 mg dose group) of patients achieved at least a 50% reduction in EASI score from baseline (EASI-50), compared with 37.5% in the placebo group.

● The EASI scores in the 300 mg and 150 mg dose groups decreased by an average of 74.4% and 74.0%, respectively, from baseline, compared with 32.9% in the placebo group.

●The mean body surface area (BSA) affected by atopic dermatitis decreased from baseline by 58.7% and 62.7% in the 300 mg and 150 mg dose groups, respectively, compared with a 28.7% decrease in the placebo group.

Skin lesions improved as early as 1 week after dosing, and the degree of improvement correlated with a rapid reduction in the intensity and frequency of pruritus.

● On Day 15, the mean weekly Pruritus Numerical Rating Scale (PNRS) scores decreased by 40.4% and 26.4% from baseline in the 300 mg and 150 mg dose groups, respectively, compared with 3.5% in the placebo group.

● On Day 29, the mean weekly PNRS decreased by 56.4% and 43.6% from baseline in the 300 mg and 150 mg dose groups, respectively, compared with 20.6% in the placebo group.

● On Day 29, the mean weekly itch frequency decreased by 57.1% and 43.0% in the 300 mg and 150 mg dose groups, respectively, compared with 19.9% in the placebo group.

The study results showed that CBP-201 was well tolerated.

● No serious adverse events (SAEs) occurred, and no adverse events related to injection site reactions or conjunctivitis/keratitis were observed.

●The proportion of patients experiencing at least one treatment-emergent adverse event (TEAE) was 85.7% in the 300 mg dose group and 62.5% in the placebo group. The incidence and severity of TEAEs were not correlated with the administered dose.

● Most TEAEs were mild in severity and mostly unrelated to CBP-201.

● Atopic dermatitis exacerbation was the only TEAE leading to discontinuation of study treatment in this study, with one patient each in the 75 mg dose group and the placebo group discontinuing treatment.

This was a randomized, double-blind, placebo-controlled, multiple ascending-dose study conducted in 31 patients with moderate-to-severe atopic dermatitis who had an inadequate response to topical corticosteroids and immunosuppressants, to evaluate the safety and efficacy of CBP-201. The trial was conducted across 10 clinical trial centers in Australia and New Zealand. In each dose cohort (75 mg, 150 mg, or 300 mg), 10 patients were randomized in a 4:1 ratio to receive either CBP-201 or placebo via once-weekly subcutaneous injections for 4 weeks, followed by a 7-week follow-up period. The primary clinical endpoint was the safety and tolerability of CBP-201, while secondary endpoints included multiple efficacy measures (Investigator’s Global Assessment [IGA] score, Eczema Area and Severity Index [EASI] score, Body Surface Area [BSA] involvement, and Peak Pruritus Numerical Rating Scale [PNRS]).

CBP-201 is a high-potency anti-IL-4Rα monoclonal antibody. IL-4Rα is a cell surface protein required for the signaling of IL-4 and IL-13, two key Th2 pro-inflammatory cytokines with significantly overlapping biological activities. CBP-201 is an innovative antibody drug independently developed by Connect Biopharma through its proprietary immune modulation technology platform. Currently in clinical development, it is intended for the treatment of moderate-to-severe atopic dermatitis and other major Th2-mediated inflammatory diseases with significant unmet clinical needs. Results from a Phase 1a clinical study involving 48 healthy subjects demonstrated that CBP-201 was well tolerated and induced a sustained and rapid reduction in serum thymus and activation-regulated chemokine (TARC/CCL17), a biomarker of Th2 activity.

In addition to CBP-201, Connect Biopharma’s other leading candidate, CBP-307, is a next-generation oral modulator of S1P1 and S1P5, expected to be used in the treatment of various autoimmune diseases, including inflammatory bowel disease, psoriasis, and multiple sclerosis. In two completed Phase 1 randomized, double-blind, placebo-controlled clinical studies, CBP-307 demonstrated favorable safety profiles, potent T-cell modulatory activity, and desirable pharmacokinetic and pharmacodynamic characteristics, indicating best-in-class potential. CBP-307 is currently undergoing two Phase 2 clinical trials to evaluate its efficacy and safety in patients with moderate-to-severe ulcerative colitis and moderate-to-severe Crohn’s disease.