Kymera Investor Day Presentation Deck slide image

Kymera Investor Day Presentation Deck

STAT3 Degraders Have Applicability in Serious Inflammatory and Fibrotic Diseases Systemic Sclerosis (SSc) Idiopathic Pulmonary Fibrosis (IPF) Atopic Dermatitis (AD) moderate-to- severe Rheumatoid Arthritis (RA) Patient Impact¹ ~85k US ~200K ROW* per year ~80k US ~180k ROW* per year ~12m ~60m ROW* per year ~2m US ~17m ROW* per year *EU, UK, Japan, China KYMERA ©2021 KYMERA THERAPEUTICS, INC. Fibrosis / Interstitial Lung Disease Autoimmune Increased STAT3 and pSTAT3 observed in SSc skin and lung biopsies • Aberrant IL6/JAK/STAT3 gene signature in biopsies from SSc patients Tocilizumab no effect on mRSS but change from baseline in FVC at week 48 (observed FVC and %pFVC) in patients with SSC/ILD ● ● ● ● STAT3 dependent cytokines (e.g. IL-11) upregulated in lung of IPF patients and are associated with disease severity IL-6/gp130 stimulation is mitogenic for IPF fibroblasts but no normal fibroblasts SoC reduces the annual rate of FVC decline STAT3 GoF pat ts exhibits signs of dermatitis TSLP receptor activates STAT3 Pruritis is linked to mechanical and IL-31R activation of STAT3 Fibrotic changes associated with AD is associated with STAT3 activation STAT3 mRNA and pSTAT3 are significantly higher in blood of RA patients STAT3 target genes (BCL3, SOCS3 and PIM1) are upregulated in early RA Constitutive STAT3 phosphorylation in circulating CD4+ T cells correlates to IL-6 levels in recent-onset RA ~30% of SoC therapies in moderate to severe RA achieve ACR70 at week 52 ¹Bionest KYMERA R&D DAY - December 16th, 2021 PAGE 69
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