YK012

hCD3EDG/hCD19 transgenic on C57BL/6 background (male; 8 weeks old)^[1]

0.125 mg/kg (Group C); 0.25 mg/kg (Group D); 0.5 mg/kg (Group E)

Day 27 to Day 73; total 15 administrations; frequency adjusted

Joint scoring showed a downward trend in joint scores of YK012 dose groups compared with the model group.
Protein level detection did not reveal differences in CRP, RF, ACPA, and SAA levels among groups.
Joint pathological staining scores showed a downward trend.
Flow cytometry demonstrated changes (fluctuations) in absolute counts of peripheral blood B cells (CD20+/B220+) and T cells (TCRβ+) and their proportions, beginning on Day 33 (6 days after first administration) and partially or fully recovering in later stages of the experiment.

HuHSC-NCG-M^[1]

G1 0.1 mg/kg; G2 0.5 mg/kg

i.v. via tail vein injection; twice a week for a total of 7 doses on D0, D3, D7, D10, D14, D17, D21

Before grouping, the average level of hCD45×hCD3 in mice was 3.31%.
After YK012 administration via tail vein injection twice a week for a total of 7 doses, there was a reduction in the number of B cells (CD79b+) in peripheral blood.
The B cell depletion effect of G1 (0.1 mg/kg) was superior to that of G2 (0.5 mg/kg).
All YK012 groups showed depletion of B cell (CD79b+) proportion and number on D1, D7, D11, D14, and D21 compared to D-5, with the degree of decrease deepening with time and number of doses.
Group G1: B cell proportion on D7 decreased; B cell proportion on D11, D14, and D21 decreased more pronouncedly.
Group G2: B cell proportion and number on D1 and B cell number on D7 decreased; B cell proportion on D7 and proportion and number on D11, D14, and D21 decreased more pronouncedly.
Compared to Group G2, Group G1 had lower B cell proportions and numbers on D11, D14, and D21, with a difference on D11.
T cell (TCRα/β+) proportion on D7, D14, and D21 increased.
No mice were euthanized due to welfare issues or unexpected death during the experiment.