KT-579 EULAR Poster Reinforces IRF5 Degradation Thesis in Lupus

Research evidence excerpt

KT-579 EULAR Poster Reinforces IRF5 Degradation Thesis in Lupus

ieving ≥50% IRF5 degradation in the spleen demonstrated activity, PT & RECOMMENDATION

with consistent and significant effects at the highest dose, establishing a clear Kymera's protein degraders may fail in the clinic.

pharmacodynamic threshold linking target engagement to efficacy. Also, kidney Kymera may require additional capital.

histology tests confirmed dose-dependent reductions in splenic plasmablasts, IgG

Price Performance - 1 Year deposition, C3 deposition, and total glomerular lesion score; each endpoint is directly

relevant to driving clinical benefit in lupus nephritis. USD

• Selectivity & Potency: KT-579 demonstrated selectivity for IRF5 across >10,000 90

detectable proteins, with no off-target degradation of other IRF family members. Potent, 80

equipotent IRF5 degradation was confirmed across all disease-relevant PBMC subsets 70

(B cells, monocytes, pDCs, mDCs) at 24 hours. 60

• Activity in SLE Patient-Derived PBMCs: In PBMCs from SLE patients, KT-579 (100 40

nM, 24h) blocked TLR-induced IRF5 nuclear translocation, significantly reduced TNFα 30

and IFNβ following TLR7/8 stimulation, and reduced plasmablast differentiation and total Jun-25 Aug-25 Oct-25 Dec-25 Feb-26 Apr-26 Jun-26

IgG production following TLR9 stimulation. Source: Bloomberg

• Broader Pathway Coverage vs Comparators: Following 4 days of oral dosing, KT-579

achieved dose-dependent IRF5 degradation in the spleen and blocked both TLR7-

and TLR9-induced cytokines (TNFα, IL-6, IL-12p40, IFNβ). The TLR7/8 small molecule

inhibitor comparator (enpatoran; M5049) did not block TLR9-induced cytokines – a direct

mechanistic differentiation consistent with IRF5's position as a convergent downstream

node of multiple endosomal TLR pathways.