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-4Rα 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 Q2Wn=57 |
150 mg Q2WN=57 |
300 mg Q4WN=56 |
PlaceboN=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 |
*P<0.05, **P<0.01, ***P<0.001 vs placebo
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-4Rα 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-4Rα 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 our Phase 2b study versus prior IL-4Rα antibody Phase 3
trials in AD.
Baseline Disease Characteristics Comparison |
Baseline Disease Characteristics |
CBP-201-WW001 (n=226) |
CBP-201-WW001China Subgroup (n=32) |
Prior IL-4Rα 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 |
- 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. Greater treatment
benefit of CBP-201 were noted among patients enrolled in the China
sub-population as indicated in the table below.
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.
- An analysis of
median percent 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 percent 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.
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 placeboBaseline EASI
tertiles: Low: ≤ 18.4, Mid: >18.4 and ≤26.4, High:
>26.4Baseline TARC tertiles: Low: ≤ 116 pg/mL, Mid: >116
pg/mL and ≤291 pg/mL, High: >291 pg/mL
- Higher treatment discontinuation
rates particularly in the active treatment arms (13%–19%) were
observed versus those of prior anti-IL-4Rα 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 our 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-4Rα 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-4Rα 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 DesignThe 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 InformationTwo 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 (CBP-201-WW001)
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 InformationConnect Biopharma’s
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.
The conference call can be accessed using the following
information:
Webcast: https://edge.media-server.com/mmc/p/2pa7xiwrU.S.:
844-646-2698Outside of U.S.:
918-922-6903Conference 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 DermatitisAtopic 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.
About CBP-201CBP-201, discovered internally
using Connect Biopharma's proprietary Immune Modulation Technology
Platform, is an antibody designed to target interleukin-4 receptor
alpha (IL-4Rα), 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 LimitedConnect
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-4Rα) — 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 Biopharma, please visit our
website at www.connectbiopharm.com.
FORWARD-LOOKING STATEMENTSConnect Biopharma
cautions that statements included in this press release that are
not a description of historical facts are forward-looking
statements. Words such as "may," "could," "will," "would,"
"should," "expect," "plan," "anticipate," "believe," "estimate,"
"intend," "predict," "seek," "contemplate," "potential," "continue"
or "project" or the negative of these terms or other comparable
terminology are intended to identify forward-looking statements.
These statements include the Company’s statements regarding the
potential of CBP-201 to achieve a differentiated, competitive, or
favorable benefit or profile including on safety, efficacy and/or
convenience, and the Company's plans to initiate a Phase 3 trial
program to further evaluate CBP-201. The inclusion of
forward-looking statements shall not be regarded as a
representation by Connect Biopharma that any of its plans will be
achieved. Actual results may differ from those set forth in this
release due to the risks and uncertainties inherent in the Connect
Biopharma business and other risks described in the Company's
filings with the Securities and Exchange Commission (“SEC”). Among
other things, there can be no guarantee that planned or ongoing
studies will be initiated or completed as planned, that future
study results will be consistent with the results to date, that
CBP-201 will receive regulatory approvals, or be commercially
successful. Investors are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of the date
hereof, and Connect Biopharma undertakes no obligation to revise or
update this news release to reflect events or circumstances after
the date hereof. Further information regarding these and other
risks is included in Connect Biopharma's filings with the SEC which
are available from the SEC’s website (www.sec.gov) and on Connect
Biopharma’s website (www.connectbiopharm.com) under the heading
"Investors." All forward-looking statements are qualified in their
entirety by this cautionary statement. This caution is made under
the safe harbor provisions of Section 21E of the Private Securities
Litigation Reform Act of 1995.
We have not conducted a head-to-head study of CBP-201 versus any
other IL-4Rα antibody. Comparisons contained herein are based on
analysis of data from separate studies. Such data may not be
directly comparable due to differences in study protocols,
conditions and patient populations. Accordingly, cross-trial
comparisons may not be reliable predictors of the relative
efficacy, safety, convenience, or competitiveness of CBP-201
compared to any other IL-4Rα antibody. The potential benefits of
CBP-201 does not imply an expectation of regulatory approval which
is solely within the authority of the FDA (or applicable foreign
regulator).
IR/PR Contacts: Lazar FINN
Partners David Carey (IR) T: +1-(212)
867-1768david.carey@finnpartners.comErich Sandoval
(Media)T:
+1-(917)-497-2867erich.sandoval@finnpartners.comCorporate
Contacts:info@connectpharm.com
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