Full Press Release Details
Connect Biopharma Reports Detailed Positive Dataset from the Global Phase 2b Trial of CBP-201 in
Adult Patients with Moderate-to-Severe Atopic Dermatitis
Phase 2b trial previously reported achievement of both primary and key secondary end points, demonstrating significant improvements in
skin clearance, disease severity, and itch compared to placebo
Additional analyses demonstrate a potentially
competitive therapeutic profile for CBP-201 300mg administered every two weeks (Q2W) or every four weeks (Q4W). Company to begin Phase 3 trial of CBP-201 in the second
Company management and Dr. Jonathan Silverberg, MD, PhD, MPH, will review additional data from the
Phase 2b trial on conference call on Wednesday January 5 at 8:30 am ET (5:30 am PST)
Data to be presented at Maui
Derm Conference January 24-28, 2022
SAN DIEGO, CA and TAICANG, SUZHOU, China - Jan. 5, 2022
- Connect Biopharma Holdings Limited (Nasdaq: CNTB) ( Connect Biopharma or the Company ), a global clinical-stage biopharmaceutical company dedicated to improving the lives of patients with chronic inflammatory diseases
through the development of therapies derived from T cell-driven research, today 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) percent 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%).
The results of the WW001 study with CBP-201 in the treatment of
moderate-to-severe AD are in line with efficacy expectations for a Phase 2b trial with the IL-4R mechanism of action, said Jonathan Silverberg, MD, PhD, MPH, Associate Professor of Dermatology, The George Washington University School of
Medicine and Health Sciences and lead author on the second WW001 Phase 2b abstract being presented at Maui Derm 2022. In addition, the favorable safety data and promising pre-specified and post-hoc analyses explaining CBP-201 s depth of
clinical response across both the moderate and more severe AD populations provide clear direction for the Phase 3 program that may bolster the strong efficacy already seen in the Phase 2b trial.
Summary of Primary Data Analyses
| Key Primary and Secondary Endpoint Results at Week 16 | ||||||||||||||||
| 300 mg Q2W n=57 | 150 mg Q2W N=57 | 300 mg Q4W N=56 | Placebo N=56 | |||||||||||||
| Least square (LS) mean % EASI score change from Baseline | -63.0 | *** | -57.5 | ** | -65.4 | *** | -40.7 | |||||||||
| EASI-50% responders | 54.4 | * | 52.6 | * | 62.5 | ** | 33.9 | |||||||||
| EASI-75% responders | 47.4 | *** | 40.4 | ** | 41.1 | ** | 14.3 | |||||||||
| EASI-90% responders | 24.6 | 14.0 | 25.0 | * | 10.7 | |||||||||||
| Investigator s Global Assessment (IGA) 0,1 % Responders | 28.1 | * | 15.8 | 21.4 | 10.7 | |||||||||||
| LS mean change (Peak Pruritus-Numerical Rating Scale) PP-NRS score from baseline | -3.56 | ** | -2.64 | -3.29 | * | -2.26 |
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-4R 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:
| Baseline Disease Characteristics Comparison | ||||||
| Baseline Disease Characteristics | CBP-201-WW001 (n=226) | CBP-201-WW001 China Subgroup (n=32) | Prior IL-4R antibody AD Ph3 trials | |||
| Median Baseline EASI | 20.1 to 22.1 | 25.9 to 32.9 | 29.4 to 31.1 | |||
| IGA score = 4 (%) | 25 to 40 | 33 to 50 | 47.2 to 48.9 | |||
| Median BSA % | 32.5 to 37.0 | 40.0 to 56.0 | 51.0 to 54.5 |
| Key Endpoint Results at Week 16 China Subgroup | ||||||||||||||||
| China Sub-population (n=32) | 300 mg Q2W (n=6 ) | 150 mg Q2W (n=11) | 300 mg Q4W (n=9) | Placebo (n=6) | ||||||||||||
| LS mean % EASI score change from Baseline | -82.9 | -60.3 | -76.1 | * | -34.9 | |||||||||||
| EASI-50 % responders | 50.0 | 72.7 | 66.7 | 33.3 | ||||||||||||
| EASI-75% responders | 50.0 | * | 54.5 | * | 55.6 | * | 0 | |||||||||
| EASI-90% responders | 16.7 | 18.2 | 33.3 | 0 | ||||||||||||
| IGA 0,1 % Responders | 33.3 | 18.2 | 22.2 | 0 | ||||||||||||
| LS mean change PP-NRS score from baseline | -2.75 | -2.12 | -3.61 | -0.78 |
*P<0.05 vs placebo; : n=4 for %EASI change from baseline.
| Post Hoc Analysis (Highest Tertile EASI Subgroup) | ||||||||||||||||
| 300 mg Q2W (n=20) | 150 mg Q2W (n=18) | 300 mg Q4W (n=13) | Placebo (n=18) | |||||||||||||
| Median Baseline EASI | 37.5 | 29.6 | 31.0 | 34.4 | ||||||||||||
| LS mean % EASI score change from Baseline | -62.9 | * | -54.9 | -81.4 | *** | -35.5 |
| Post Hoc Analysis (Highest Tertile TARC Subgroup) | ||||||||||||||||
| 300 mg Q2W (n=16) | 150 mg Q2W (n=20) | 300 mg Q4W (n=14) | Placebo (n=19) | |||||||||||||
| Median Baseline EASI | 34.4 | 27.2 | 28.1 | 26.2 | ||||||||||||
| LS mean % EASI score change from Baseline | -61.7 | ** | -63.2 | ** | -83.0 | *** | -28.6 |
*P<0.05, **P<0.01, ***P<0.001 vs placebo
Baseline EASI tertiles: Low: 18.4, Mid: >18.4 and
Baseline TARC tertiles: Low:
116 pg/mL, Mid: >116 pg/mL and 291 pg/mL, High: >291 pg/mL
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-4R antibody therapy in future studies of patients with higher baseline disease severity.
The results of the additional analyses provide details of the potential significant benefits of CBP-201 in the
treatment of adult patients with moderate-to-severe AD, despite having enrolled a relatively less severe patient population, said Zheng Wei, PhD, Co-Founder and CEO of Connect Biopharma. We are very encouraged by the findings from the additional analyses and remain confident on the potential for a highly competitive efficacy and safety profile for CBP-201 coupled with a more convenient and differentiated Q4W dosing schedule. We look forward to leveraging the insights from the additional analyses as we initiate a Global Phase 3 clinical trial program in the
second half of 2022.
These new results add to the body of evidence that CBP-201 has the potential to
provide clinically meaningful benefit to adult patients with moderate-to-severe AD, said Dr. Bruce Strober, Clinical Professor of Dermatology, Yale University
School of Medicine and lead author on the first of two WW001 Phase 2 trial abstracts to be presented at Maui Derm 2022 in January. In addition to efficacy data that look at least comparable to current
anti-IL-4R therapy, CBP-201 may be able to be dosed every four weeks which could reduce patients treatment burdens and aid in treatment adherence. I look
forward to the planned Phase 3 trial program of CBP-201 commencing in the second half of 2022.
CBP-201 Global Phase 2b Clinical Trial Design
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.
Maui Derm Presentation Information
Two abstracts related
to the CBP-201 Phase 2 trial have been accepted for presentation at the 18th Annual Maui Derm meeting, taking place January 24-28, 2022.
Efficacy and Safety of CBP-201 in Adults with
Moderate-to-Severe Atopic Dermatitis (AD): A Phase 2b, Randomized, Double-blind, Placebo-controlled Study
The Effect of Baseline Disease Characteristics on
Efficacy Outcomes: Results from a Phase 2b, Randomized, Double-blind, Placebo-controlled Trial (CBP-201-WW001)
Conference Call Information
management team, along with Dr. Jonathan Silverberg, will host a conference call and webcast today to review data from its global Phase 2 trial of CBP-201 in patients with
moderate-to-severe AD, beginning at 8:30 am Eastern Time.
call can be accessed using the following information:
Outside of U.S.: 918-922-6903
Conference ID: 7998162
The webcast will also be
available in the Investors section of the Company s website following the completion of the call.
About Atopic Dermatitis
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. It is characterized by skin barrier disruption and immune dysregulation. Estimates of prevalence of AD in China show an increase over time and recent longitudinal studies have reported a dermatologist-diagnosed prevalence
of 7.8% in Chinese outpatients visiting tertiary hospitals. In the United States, it is estimated that 26.1 million people have AD, of which 6.6 million have
moderate-to-severe disease. Further, 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.
CBP-201, discovered internally using Connect Biopharma s proprietary Immune Modulation Technology Platform,
is an antibody designed to target interleukin-4 receptor alpha (IL-4R ), which is a validated target for the treatment of several inflammatory diseases, including
atopic dermatitis (AD). CBP-201 was well tolerated and showed evidence of clinical activity in a Phase 1b clinical trial in adult patients with
moderate-to-severe atopic dermatitis, suggesting a potential for a differentiated efficacy profile compared with data from clinical trials of the current biologic
standard of care therapy. CBP-201 has been evaluated in a global Phase 2b trial in adult patients with moderate-to-severe atopic
dermatitis (NCT04444752); in a China specific pivotal trial in adults with moderate-to-severe atopic dermatitis (NCT05017480); in a Phase 2b trial in adult patients with
moderate-to-severe persistent asthma (NCT04773678); and in a Phase 2b trial in adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP) (NCT04783389).
About Connect Biopharma Holdings Limited
Biopharma Holdings Limited is a global clinical-stage biopharmaceutical company dedicated to improving the lives of patients living with chronic inflammatory diseases through the development of therapies derived from our T cell-driven research.
Our lead product candidate, CBP-201 an antibody designed to
target interleukin-4 receptor alpha (IL-4R ) has been in clinical trials for the treatment of AD, asthma, and CRSwNP. Our second lead product candidate, CBP-307 a modulator of a T cell receptor known as sphingosine 1-phosphate receptor 1 (S1P1) has been in clinical trials for the treatment of ulcerative colitis
(UC) and Crohn s disease (CD). Furthermore, we have started the clinical development of an additional product candidate, CBP-174 a peripherally acting antagonist of histamine receptor 3 for
the treatment of pruritus associated with AD.
With clinical development activities in the United States, China, Europe, and Australia, and operations in
those geographies as well as Hong Kong, Connect Biopharma is building a rich global pipeline of internally designed, wholly owned small molecules and antibodies targeting several aspects of T cell biology. For additional information about Connect