Innovative protein degradation therapy received first proof of concept in human body, which can reduce target protein level by 90%

Today, Kymera Therapeutics announced that its investigational oral small-molecule protein degradation drug KT-474 has achieved positive interim results in the single-dose escalation (SAD) portion of the phase 1 clinical trial

At the same time, Kymera announced that the multiple dose escalation (MAD) part of the KT-474 phase 1 clinical trial has been released by the FDA

IRAK4 is a key protein in Toll-like receptors (TLRs) and IL-1 receptor-mediated inflammation

KT-474 is a potential "first-in-class" IRAK4 oral protein degradation agent developed by Kymera

Compared with antibody therapy targeting cytokines that activate TLRs and IL-1 receptors, targeting IRAK4 can simultaneously block the signaling pathways of multiple inflammatory cytokines

▲The degradation of IRAK4 can more effectively block the signal pathway mediated by TLRs/IL-1 receptors (picture source: reference [2])

In the SAD part of this clinical trial, healthy volunteers took a placebo or different doses of KT-474

▲Single dose of KT-474 reduces IRAK4 levels quickly and lastingly (picture source: reference [2])

In the cohort taking a single 300 mg dose of KT-474, the median IRAK4 level after 48 hours decreased by 90% compared with baseline compared with baseline, and the placebo group increased by 16% (p<0.

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Reference materials:

[1] Kymera Therapeutics Announces Positive Interim Results from Single Ascending Dose Phase 1 Trial of KT-474 Demonstrating Degrader Proof-of-Mechanism.

[2] KT-474 Phase 1 Update Call Presentation.