Connect Biopharma Holdings Limited reported detailed positive data from the global Phase 2b clinical trial of CBP-201 administered subcutaneously (SC) to adult patients with moderate-to-severe atopic dermatitis (AD) (WW001) (NCT04444752). The Company announced topline results from the Phase 2b trial on November 18, 2021 indicating that all three CBP-201 arms (300mg Q2W, 150mg Q2W or 300mg Q4W) met the primary endpoint of eczema area and severity index (EASI) reduction from baseline at Week 16 and were statistically superior to placebo. The announcement noted that multiple key secondary endpoints were also met with CBP-201.

CBP-201 was also observed with favorable safety data and, versus placebo, demonstrated a similar incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEAEs leading to study drug discontinuation. For adverse events (AEs) of special interest (AESI) among patients receiving CBP-201, there were low reported incidences of injection site reactions (1.8%) and conjunctivitis (3.5%). Since the CBP-201 Phase 2b trial occurred during the COVID-19 pandemic and the patient population recruited had a markedly lower AD disease severity and higher patient discontinuation rate relative to previous IL-4Ra antibody Phase 3 trials, additional analyses were performed to determine the effects of these factors on the magnitude of the treatment benefit observed with CBP-201 in the Phase 2b study.

Additional Data Analyses – Key Findings from A Priori and Post-Hoc Analyses: Compared to prior IL-4Ra antibody trials in AD, patients enrolled across all treatment groups in this study had significantly lower disease severity at baseline. The lower severity of disease in the overall study population could have contributed to the lower percentage EASI score changes from baseline across all treatment groups observed in Phase 2b study versus prior IL-4Ra antibody Phase 3 trials in AD. In the China sub-population (n=32), a pre-defined analysis performed to support ongoing discussions with regulatory authorities in China, versus the overall trial population, patients had a higher median baseline EASI score, greater proportion of IGA score=4 and a higher BSA involvement than the overall trial population.

An analysis of median percentage EASI reduction from baseline which reduces the impact of the low median EASI baseline and the non-normal distribution of patients' AD disease severity observed in this trial, showed greater reductions (79.3%, 64.7%, 72.4% for 300 mg Q2W, 150 mg Q2W, 300 mg Q4W, respectively vs. 41.0% in Placebo) compared to the LS means percentage EASI reduction from baseline reported above (n=226). In an exploratory post-hoc analysis of patients with higher disease severity at baseline based on EASI score (n=69), relative to the overall trial population, results showed both greater reduction of EASI score from baseline and a lower placebo response.

Similarly, a post-hoc analysis of patients (n=69) with higher baseline thymus and activation-regulated chemokine (TARC or CCL17), a biomarker associated with disease activity in patients with AD, vs. the overall patient population in this trial, showed that they achieved greater EASI reduction and had a lower placebo response, compared to the overall population. Higher treatment discontinuation rates particularly in the active treatment arms (13%–19%) were observed versus those of prior anti-IL-4Ra Phase 3 trials (6.3–9.5%).

The vast majority of the discontinuations in the Phase 2b study were due to patients withdrawing consent or patients being lost to follow-up, and it is likely that movement restrictions related to the COVID-19 pandemic contributed to the higher observed rates. None of the discontinuations in Phase 2b study were attributable directly to COVID-19 infection. These additional analyses demonstrate that the significant treatment benefit seen in the primary analyses for CBP-201 are markedly higher in patients with higher baseline AD disease severity based on EASI score and TARC or CCL17.

These findings demonstrate that CBP-201 has the potential to show a superior efficacy profile against current IL-4Ra antibody therapy in future studies of patients with higher baseline disease severity. The global Phase 2b clinical trial, “A Randomized, Double-Blind, Placebo-Controlled Multi-Centered Study of the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of CBP-201 in Adult Subjects with Moderate to Severe Atopic Dermatitis,” enrolled 226 patients (ages 18–75 years) throughout the United States, China, Australia and New Zealand. Patients were randomized to one of three CBP-201 treatment groups or the placebo group.

The CBP-201 treatment groups all received a 600 mg loading dose on Day 1 and then received 300 mg Q2W, 150 mg Q2W or 300 mg Q4W. The treatment period was 16 weeks, and all patients were followed for an additional period of 8 weeks. CBP-201 and placebo were administered via SC injection.

The primary efficacy endpoint was percentage reduction in the EASI score from baseline to Week 16 for each CBP-201 group compared with the placebo group; the key secondary endpoints were the proportion of patients with an IGA score 0 or 1 and a reduction of =2 points at Week 16; the proportion of patients achieving EASI-50, EASI-75 or EASI-90 from baseline at Week 16; and change from baseline to Week 16 in weekly average PP-NRS. Safety assessments included reported AEs, vital signs, physical examinations and injection site changes; laboratory and electrocardiogram evaluations; and the number of patients displaying anti-drug antibodies. In the coming months, Connect Biopharma intends to discuss the CBP-201 data with the FDA and other health authorities and seek feedback on its planned Phase 3 trial program in adult patients with moderate-to-severe AD.

The Company plans to commence enrollment in the second half of 2022.