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Statement
| 1.Product:FB825 Anti-CεmX monoclonal antibody
2.Mass production date:NA
3.Effect on company finances and business:
(1)New drug name or code:FB825 Anti-CεmX monoclonal antibody
(2)Purpose:A.To treat moderate-to-severe atopic dermatitis, allergic asthma
and other IgE-mediated diseases
B.Information Website:clinicaltrials.gov
(3)Planned development stages：Subcutaneous injection clinical bridging
study, Phase 2b clinical study, Phase 3 clinical study, BLA application
(4)Current development stage:
A.File application/approved/disapproved/Each of clinical trials (include
interim analysis):
(A)Clinical Trial Design
a.Protocol Title：A Randomized, Double-Blind, Placebo-Controlled Phase
Ⅱ Study to Evaluate. Efficacy, Pharmacokinetics, and Safety of
Multiple Intravenous Doses of FB825 in Adults with Atopic Dermatitis
b.Study Purpose：To evaluate the efficacy of FB825 as monotherapy
without the use of topical corticosteroid in treatment of moderate
-to-severe atopic dermatitis, of multiple intravenous (IV) doses for
16 weeks (q4w) in subjects with atopic dermatitis
c.Phase of Study：Phase 2a Clinical Trial
d.Investigational product：FB825 Anti-CεmX monoclonal antibody
e.Indication：Moderate-to-severe atopic dermatitis
f.Endpoints：
Primary endpoints：Mean change from baseline in EASI at week 16
Secondary endpoints: The mean percentage change from baseline in EASI
score, vIGA-AD at Weeks 2, 4, 8, 12, 16, 20 and 24; the
pharmacokinetics (PK) profiles of multiple IV doses of FB825; the
incidence of adverse events
g.Number of subjects enrolled：99 subjects
(B)Primary and secondary endpoints and the statistical results：
a.Primary endpoint and the statistical results:
(a)According to the data provided by the international CRO, the
biochemical analyses on all samples after the study completion
showed that 2/3 of the patients were not targeted population. The
analysis on the two key biomarkers in moderate-to-severe AD
including thymus and activation regulated chemokine (TARC) and
immunoglobin E (IgE) showed exceedingly lower value of which the
baseline TARC level of 2/3 of the study subjects was lower than
700 pg/ml (1,953 - 6,147 pg/ml in Dupixent's studies; baseline
mean serum IgE level was 569 IU/ml (2,451 - 10,754 IU/ml in
Dupixent's studies). Therefore, the analysis on the primary
endpoint by including the above non-target patients was not
statistically significant and the evaluation on the non-target
population cannot provide clinically meaningful data.
(b)In the further analysis, among the remaining 1/3 potential target
population (baseline TARC > 700 pg/ml), 53.8% of patients in FB825
group reached EASI 75 (proportion of patients with 75% reduction
in EASI which is a key endpoint in most of the phase 3 studies) vs.
29.4% in placebo group (LOCF). FB825 has met the anticipated
treatment efficacy in the potential target population, which
supports to proceed with the subsequent clinical trials
(c)The LS mean change from baseline in EASI at week 16 (LOCF) in the
potential target population showed -7.8 vs. -5.9 (FB825 vs.
placebo). The mean percentage change from baseline in EASI at week
16 (LOCF) in the potential target population demonstrated -54.9%
vs. -35.2% (FB825 vs. placebo). The trend in disease improvement in
both endpoints is consistent with that in EASI-75. The data have
been provided to the international partner for reference.
(d)The trial was executed by the international CRO. The enrollment of
a high proportion of the non-target patients was probably impacted
by the pandemic.
(i)The patient enrollment (from Jul 2020) in the US started during
the outbreak of the pandemic. The targeted moderate-to-severe
AD patients are with long-term immunosuppressant medication so
they tend not to keep the regular visits to the health
practitioners during the pandemic. According to the Dutch survey
on approximately 54,000 AD patients published on JAAD
International in March 2022, the moderate-to-severe AD patients
had significantly higher anxiety in face of the pandemic. To
avoid COVID-19 infection, they more often chose not to contact
a doctor when having health problems (p<0.001).
(ii)To achieve the recruitment timeline within 1 year, referral
mechanism was implemented in this Phase 2a study. Over 50% of
the subjects were enrolled by referral and those patients were
new to the clinical sites and lack of historical medical record
for disease diagnosis and impacted the enrollment of targeted
patients.
b.Secondary endpoint and the statistical results: Apart from the above
disclosed data in EASI-75 and the mean percentage from baseline in
EASI at week 16, the remaining secondary endpoints and results with
biomarkers remain undisclosed for the consideration of future patent
filing.
c.Exploratory endpoint and the statistical results: Exploratory
endpoints and results with biomarkers remain undisclosed for the
consideration of future patent filing.
d.Safety evaluation results: FB825 has been demonstrated the
consistently good safety profile and no drug-related serious adverse
events occurred during the treatment. The incidence of the treatment-
emergent adverse event was 36% vs. 52% (FB825 vs. placebo) and the
drug-related treatment-emergent adverse event was 12.0% vs. 16.7%
(FB825 vs placebo).
(C)The results of a single clinical trial (including the p value or
whether there is statistical significance in primary, secondary
endpoints) shall not be sufficient to reflect the success or failure
of the new drug in the future development. The investors shall be
careful in judgement and investment.
B.Once disapproved by competent authority or each of clinical trials (include
interim analysis) results less than statistically significant sense, the
risks & the associated measures the Company may occur:
(A)This is the first-in-patient Phase 2a study of FB825 in the moderate-to
-severe atopic dermatitis patients in the U.S. for exploration on
efficacy. The main purpose of the study was to explore the clinical
efficacy, safety and pharmacokinetics of FB825 in moderate-to-severe AD
patients in the U.S., of which the results provide a reference for the
subsequent trial design.
(B)This study enrolled moderate-to-severe severity of AD patients in the
U.S. and the blood samples were collected during the treatment visits
and follow-up visits for biochemical analysis after the completion of
the study. This is to observe the correlation between the treatment
efficacy and the change in the important biomarkers. This will be an
important basis for the subsequent clinical trial design for FB825.
(C)This exploratory study in the moderate-to-severe atopic dermatitis
patients showed that the treatment efficacy in EASI-75 of FB825
(53.8%), as a monotherapy without topical corticosteroid, is comparable
to the blockbuster drug, Dupixent (44% and 51% in EASI-75 in two phase
3 studies). Dupixent is dosed every two weeks, while FB825 is dosed
every 4 weeks with dosing frequency advantage. No drug-related serious
adverse event occurred in FB825 treatment group and the pharmacokinetic
profile is also well-supported. The subsequent trials will be designed
based on the efficacy, safety and PK observed in the analysis on the
target population.
(D)According to the exploration results in this Phase 2a study, FB825 has
met the anticipated treatment efficacy in the potential target
population, which supports to proceed with the subsequent clinical
trials.
C.After obtaining official approval or the results of statistically
significant sense, the future strategy: N/A
D.Accumulated investment expenditure incurred:Undisclosed
(5)Upcoming development plan:Subcutaneous injection clinical bridging study
A.Scheduled completion date:The actual timeline will be subject to the
review and approval by the health authorities.
B.Estimate responsibilities:None
(6)Market:Atopic dermatitis is a chronic inflammatory dermatological disease
with heterogeneity, featured with itching and eczematic condition. AD has
been a common dermatological disorder in the developed countries. Up to 5%
of the adults population suffer from such disease in the U.S., Canada,
Europe and Japan.
4.Any other matters that need to be specified:
(1)According to Article 2 under Guidelines by Taipei Exchange on the Material
Information Announced by Listed and OTC Companies, new drug development
companies shall make public announcement when filing application for
clinical trials or new drug application to domestic or overseas regulatory
authorities, receiving approval or disapproval, obtaining the statistical
date of endpoints in each clinical trial (including interim analysis), or
receiving approval or disapproval on drug license application.
(2)It takes considerable time and expenses to develop a new drug of which
success can't be guaranteed. Investors shall bear such investment risk
that warrants careful assessment before making investment decisions.
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