Tu154 - Efficacy and Safety of Ebdarokimab, in Subjects with Moderate to Severe Ulcerative Colitis: Results from a Randomized, Double-blind, Placebo-controlled, Single-dose Escalation Phase Ib Clinical Study

1. Hong Yang – merry91928@qq.com – Peking Union Medical College Hospital
2. Yu Xia – michelle.xia@akesobio.com – Akeso Biopharma, Inc., Zhongshan, China
3. Max Wang – max.wang@akesobio.com – Akeso Biopharma, Inc., Zhongshan, China
4. Baiyong Li – baiyong.li@akesobio.com – Akeso Biopharma, Inc., Zhongshan, China
5. Xiang Ni – jason.ni@akesobio.com – Akeso Biopharma, Inc., Zhongshan, China
6. Guoqin Wang – guoqin.wang@akesobio.com – Akeso Biopharma, Inc., Zhongshan, China
7. Li Zhang – li.zhang@akesobio.com – Akeso Biopharma, Inc., Zhongshan, China

Background
Interleukin-12 (IL-12) and interleukin-23 (IL-23) are two essential cytokins involved in the immune-mediated inflammatory disorders of Ulcerative Colitis (UC). Ebdarokimab (AK101) is a fully human monoclonal antibody (mAb) targeting IL-12/IL23 pathway, and being developed for treating UC, has showed excellent safety and tolerability in pre-clinical studies.

Methods
A total of 34 UC subjects (male and female) with age ranging from 18 to 65 years were enrolled, 26 subjects received Ebdarokimab and 8 subjects received placebo. The study includes subcutaneous (SC) and intravenous (IV) groups. Subjects in the SC groups were given a single dose of 270mg or 540mg respectively. Subjects in the IV groups received 4mg/kg, 6mg/kg or 9mg/kg of Ebdarokimab at week 1 (D1) for the dose escalation phase of this study.

Results
26 subjects were treated with Ebdarokimab, 10(83.3%) of 12 subjects in the SC group experienced treatment emergent adverse events (TEAE); 9(64.3%) of 14 subjects in the IV group; 2(25%) of 8 subjects in the placebo group experienced TEAEs. Most TEAEs /TRAEs were mild and moderate. No death was reported.

The median Tmax of Ebdarokimab SC was approximately 7 days. The absolute bioavailability was approximately 59.4% in 270mg group. The mean Vz, CL, and half-life ranged from 10.3 to 11.7L,0.37 to 0.46L/day,17.4 to 21.4Day following a single dose IV, respectively. The exposure of Ebdarokimab increased dose proportionally in the dose range from 4mg/kg to 9mg/kg. There was no treatment-related ADA-positive in the evaluated subjects.

Conclusion
Ebdarokimab was generally safe and well tolerated, and indicated dose-proportional exposures.