Slide 1: The IRAK-4 inhibitor Emavusertib (CA-4948) for the treatment of primary CNS lymphoma
2022 SNO Annual Meeting, Tampa The IRAK-4 inhibitor Emavusertib (CA-4948) for the treatment of primary CNS lymphoma (PCNSL) Abstract EXTH-93 Christina von Roemeling, PhD
Slide 2: Project Overview
Project Overview • Demonstrate MyD88 activation in PCNSL • Determine CNS concentrations of Emavusertib (CA-4948) & determine if within therapeutic range • Assess Emavusertib (CA-4948) anti-tumor efficacy in PCNSL preclinical models
Slide 3: MYD88 is a driver of lymphomagenesis
MYD88 is a driver of lymphomagenesis Created with BioRender.com Haematologica (2019) 104, 12: 2337-2348
Slide 4: Emavusertib (CA-4948): A novel small molecule IRAK4 Kinase Inhibitor
Emavusertib (CA-4948): A novel small molecule IRAK4 Kinase Inhibitor • First-in-class inhibitor • Good oral bioavailability Human Murine • High binding affinity to human IRAK4 (23 nM), high predicted binding affinity to murine IRAK4 • Well tolerated; safety profile allows long-term treatment and com
Slide 5: Emavusertib in B Cell Cancers
Emavusertib in B Cell Cancers Monotherapy Percent Change in Tumor Burden from Baseline (6 patients treated for ~ 1 year or longer) 20 6 patients were treated with emavusertib for 10 ~1 year or longer Percent Change from Baseline in Tumor Burden (%) 0 • 3 patients ongoing with treatment with -10 -20
Slide 6: MYD88 activation in patient PCNSL
MYD88 activation in patient PCNSL
Slide 7: Emavusertib reaches therapeutic doses in CNS
Emavusertib reaches therapeutic doses in CNS Preclinical model sensitivity to CA-4948 LC-MS/MS detection of CA-4948 in murine CNS CA-4948 Conc. (ug/mL or ug/G) Plasma human murine 100 CSF Brain (naive) 10 Brain (A20 tumor) SU-DHL-4 Cell Count (fold change) OCI-LY3 Cell Count (fold change) MYD88 L265
Slide 8: Emavusertib: preclinical anti-tumor activity in CNS
Emavusertib: preclinical anti-tumor activity in CNS Improved survival in preclinical PCNSL CA-4948 reduces in vivo tumor proliferation <0.0001 80 A20 Ki67 Index 60 CA-4948 Med. Survival 40 vehicle 44.0 days p=0.010 p=0.044 50 mg/kg 47.0 days 100 100 mg/kg 70.5 days 20 % survival (OCI-LY3) 80 0 48 A-
Slide 9: Thank you
Thank you Duane A. Mitchell, M.D., Ph.D. Bently Doonan, M.D. Kelena Klippel, M.S. Daniel Schulz, Ph.D. Lan Hoang-Minh, Ph.D. Vrunda Trivedi, M.S. Rylynn Russell Chenglong Li, Ph.D. Elizabeth Ogando-Rivas, M.D. The Florida Center for Brain Tumor Research UF Drug Development Core Han W. Tun, M.D. CTIM