Kymera Investor Day Presentation Deck
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Summary of Phase 1 KT-474 SAD/MAD
Healthy volunteer SAD dose escalation completed; MAD enrolled through Cohort 4 (200 mg), with
proof of mechanism (IRAK4 degradation) and proof of biology (broad inhibition of cytokine
induction) established in SAD and at substantially lower doses in MAD
Marked reduction of IRAK4 protein in blood and skin to near LLOQ of highly quantitative and
sensitive mass spectrometry assay achieved at a dose of 100-200 mg daily x 14 days
Strong and broad inhibition of whole blood ex vivo cytokine induction in MAD comparable to what
was seen at highest SAD dose (1600 mg) demonstrated in association with >90% IRAK4 reduction
in monocytes at 100 mg daily dose
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While cytokine results at 200 mg not currently available, even greater inhibition anticipated at that dose
given the substantial increase in plasma exposure and tissue degradation (e.g. skin) and 94% IRAK4
reduction in monocytes
High sensitivity CRP levels in plasma too noisy over time to detect meaningful changes
Prolonged suppression of IRAK4 in blood and skin for at least 14-21 days with KT-474 multi-
dosing shown to be safe and well-tolerated
On track to initiate open-label cohort in HS and AD patients in Q1 next year with data read-out
planned for mid-year, followed thereafter by start of Phase 2 studies in multiple indications
KYMERA ©2021 KYMERA THERAPEUTICS, INC.
KYMERA R&D DAY - December 16th, 2021
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