Oneness received the notification by the international CRO on the unblinded data of FB825 Phase 2a study in moderate-to-severe atopic dermatitis in the U.S.

Published Date:2022-05-02

Original Link:https://www.onenessbio.com/en/news_detail163_2.htm

Statement
No	1	Date of announcement	2022/05/02	Time of announcement	20:10:48
Subject	Oneness received the notification by the international CRO on the unblinded data of FB825 Phase 2a study in moderate-to-severe atopic dermatitis in the U.S.
To which item it meets	paragraph 10			Date of events	2022/05/02
Product:FB825 Anti-CεmX monoclonal antibody Mass production date:NA 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. 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.