Curis, Inc. · NASDAQ:CRIS
Curis — Technical Presentation (August 2024)
14 slides from Curis's technical presentation, August 2024
Slide 1: Targeting IRAK4 as Novel Therapy in Primary CNS Lymphoma
Targeting IRAK4 as Novel Therapy in Primary CNS Lymphoma Christopher D’Angelo, MD Assistant Professor, Hematology/Oncology Fred and Pamela Buffett Cancer Center University of Nebraska Medical Center
Slide 2: Disclosures
Disclosures • Consulting: Abbvie, Genmab, Bristol Myers Squibb, Curis Inc • Research: Bristol Myers Squibb, Abbvie, Genmab, Fate Therapeutics, Curis Inc
Slide 3: Objectives
Objectives • Discuss IRAK4 and the rationale for targeting IRAK4 in treating PCNSL • Describe preliminary data on safety and efficacy for emavusertib + ibrutinib in r/r PCNSL resistant to BTKi
Slide 4: PCNSL Outcomes: Room for Improvement
PCNSL Outcomes: Room for Improvement Relapsed/Refractory Newly Diagnosed Age >60 PFS 36mo: 37% PFS <5mo David et al, AJH 2023 Lagner-Lemercier, Neuro Oncol, 2016
Slide 5: Relapsed/Refractory PCNSL Trials
Relapsed/Refractory PCNSL Trials Drug ORR (CR) PFS Ibrutinib1 77% (39%) 4.6mo Pomalidomide/dex2 48% (32%) 5.3mo Temozolomide3 31% (25%) 2.8mo revlimid-rituximab4 35% (25%) 7.8mo 1Grommes et al, Cancer Discovery 2017, 2Tun et al, Blood 2019, 3Reni et al, Br J Cancer 2007, 4Ghesquieres et al, Annal On
Slide 6: IRAK4 Signaling in Lymphoma
IRAK4 Signaling in Lymphoma The“myddosome”: activates NF-kB and present in PCNSL TME beyond cancer cells: astrocytes and immune cells Von Roemling et al Clin Cancer Res 2023
Slide 7: IRAK4 is synergistic with BTKi
IRAK4 is synergistic with BTKi emavusertib + ibrutinib blocking both BCR and TLR pathways has been demonstrated to be better than blocking either one alone • IRAK4 inhibition synergizes with BTK inhibition to promote killing of ABC-DLBCL1 • Concurrent treatment with IRAKi and ibrutinib was significa
Slide 8: TakeAim Lymphoma
TakeAim Lymphoma Open-label expansion trial evaluating the safety, PK/PD, and clinical activity of emavusertib (CA-4948) + ibrutinib in R/R primary CNS lymphoma NCT03328078 Complete Complete Enrolling Part A1 Part A2 Combination Dose Part B Monotherapy Dose PCNSL Expansion Cohort Escalation (MTD) Es
Slide 9: TakeAim Lymphoma: Study Design, PCNSL Expansion
TakeAim Lymphoma Study Design: PCNSL Expansion Patient Population Study Treatment Endpoints 28-day Cycle Emavusertib • R/R PCNSL exposed/refractory Primary: 100-200 mg BID to BTKi • Safety (AEs) • Absence of residual grade ≥2 + Secondary: toxicity from prior therapy Ibrutinib • ORR, DOR, DCR, PFS, O
Slide 10: Well-tolerated and Manageable Adverse Event Profile
TakeAim Lymphoma Well-tolerated and Manageable Adverse Event Profile at Multiple Dose Levels Grade 3+ Treatment-Related 100 mg 200 mg 300 mg Total Adverse Event Ocurred in >1 Patient BID+IBR BID+IBR BID+IBR N (%) (N=2) (N=10) (N=7) (N=19) # patients having grade 3+ TRAEs 1 (50) 7 (70) 6 (86) 14 (74)
Slide 11: Preliminary Efficacy Results in PCNSL Population
Preliminary Efficacy Results in PCNSL Population NHL Population: Duration PCNSL Population * Indicates patient is ongoing with treatment Grommes, C. (2023). American Society of Hematology (ASH) Annual Meeting, 2023.
Slide 12: PCNSL patient achieved 95.3% PR on ibrutinib + emavusertib
PCNSL patient achieved 95.3% PR on ibrutinib + emavusertib Emavusertib + Ibrutinib C1D1 12/26/2023 Dec 19, 2023 Jan 18, 2024 Feb 19, 2024 (Day 24) Relapsed PR PR on ibrutinib *as of April 1, 2024
Slide 13: Conclusions
Conclusions • R/R PCNSL carries a poor prognosis • IRAK4 signaling is increased in PCNSL, targeted inhibition with emavusertib + ibrutinib shows strong preclinical efficacy • Preliminary data of combo IRAK4 + BTKi demonstrates safety, with encouraging responses in BTKi exposed/refractory • Study is
Slide 14: University of Nebraska Medical Center
Ss University of Nebraska Medical Center’ BREAKTHROUGHS FOR LIFE.” Nebraska Medical Center