Curis, Inc. · NASDAQ:CRIS
Curis — EHA 2021
18 slides from Curis's conference presentation, Jun 11, 2021
Slide 1: Connecting Hematology - For Clinical and Research Excellence
| Connecting Hematology - For Clinical and Research Excellence
Slide 2: Phase 1 Dose Escalation Trial of Oral IRAK4 Inhibitor CA-4948 in AML or MDS
A PHASE 1, DOSE ESCALATION TRIAL WITH NOVEL ORAL IRAK4 INHIBITOR CA-4948 IN PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA OR MYELODYSPLASTIC SYNDROME – INTERIM REPORT Guillermo Garcia-Manero, MD1, Stefano R. Tarantolo, MD2, Amit Verma, MD3, James Dugan, MD4, Eric S. Winer, MD5, Aristoteles Giagounidis, M
Slide 3: Disclosures
DISCLOSURES Research support from: Curis, Astex, Abbvie, BMS, Jazz, Novartis, Aprea, ALX, Gilead, Seattle Genetics
Slide 4: Introduction
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS TLR Pathway Introduction TLR1 TLR2 TLR4 TLR5 TLR6 • Interleukin-1 receptor associated kinase 4 (IRAK4) plays an essential role in toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) signaling pathways Endosome TLR7 TLR8 TLR9 • These pathways are fr
Slide 5: CA-4948: A novel small molecule IRAK4 inhibitor
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS CA-4948: A novel small molecule IRAK4 inhibitor IRAK4/CA-4948 Co-crystal Structure • First-in-class IRAK4 inhibitor in oncology • Inhibits hematological malignancies that are driven by over-activity of the TLR/IL-1R pathway, which is dependent on IRAK4 • C
Slide 6: CA-4948 targets IRAK4-L, a key driver of leukemia
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS CA-4948 targets IRAK4-L, a key driver of leukemia IRAK4-L is oncogenic CA-4948 targets IRAK4-L CA-4948 Blocking IRAK4-L treatment reduces reduces formation of leukemic blasts leukemia colonies in patient-derived in preclinical studies1 xenografts2 IRAK4-L
Slide 7: CA-4948 reduces tumor burden in preclinical models
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS CA-4948 reduces tumor burden in preclinical models Xenografts treated with CA-4948 Treatment with CA-4948 CA-4948 is more active in maintained normal spleen size prevented leukemic engraftment cell lines overexpressing IRAK4-L (surrogate for leukemic burde
Slide 8: Study design: multicenter single arm Phase 1 dose escalation study
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Study design: multicenter single arm Phase 1 dose escalation study of CA-4948 monotherapy in adult patients with AML or high risk MDS 200 mg 300 mg 400 mg 500 mg BID BID BID BID 3+3 design; continuous 28-day cycles in the absence of unacceptable toxicity o
Slide 9: Patient eligibility
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Patient eligibility Inclusion: • ≥ 18 years of age • ECOG ≤ 2 • hrMDS or AML (WHO 2016 classification): - R/R after failing at least 1 standard treatment Exclusion: • Acute promyelocytic leukemia (APL, M3) • Active central nervous system leukemia • Blast s
Slide 10: Baseline characteristics of patients who received CA-4948
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Baseline characteristics of patients who received CA-4948 Characteristics Patients (n=22) Female n (%) : Male n (%) 5 (23):17 (77) Age (yrs): median (range) 74 (32 - 87) 22 subjects treated1 White 18 (82) Race, n (%) African American 1 (4) Not reported 3 (
Slide 11: Treatment-related adverse events occurring in ≥ 2 patients
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Treatment-related adverse events occurring in ≥ 2 patients Per patient, highest grade 200 mg BID 300 mg BID 400 mg BID 500 mg BID All (n=3) (n=6) (n=10) (n=3) (n=22) Grade Grade Grade Grade All Grades Grade 3 or 4 Preferred Terms All 3 or 4 All 3
Slide 12: Predictable clinical PK of CA-4948
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Predictable clinical PK of CA-4948 CA-4948 mean ± SE plasma concentration versus time profile following BID oral administration • Half-life ~6 hours 8,000 Mean 200mg Mean 300mg Mean 400mg MeanSE CA-4948 Plasma Concentration (ng/mL) Mean 500mg • Rapidly ab
Slide 13: Treatment duration and patient response to CA-4948
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Treatment duration and patient response to CA-4948 17 evaluable patients, including 5 with responses, and 1 patient who proceeded to SCT Best Response hrMDS (n=9) CR 1 mCR 2 SD 4 PD1 2 2 AML (n=8) CRi 1 PR 1 SD 3 PD1 3 Best response 1) Includes two patient
Slide 14: CA-4948 reduces marrow blasts in 10 of 12 patients
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS CA-4948 reduces marrow blasts in 10 of 12 patients with elevated blast counts at baseline Dose level Diagnosis Baseline blast Post-tx blast Change (%) (%) hrMDS 11 2 -82% 200 mg BID AML 24 9 -63% hrMDS 4 2 -50% hrMDS 4 4 0% AML 23 0 -100% AML 39 18 -54% 30
Slide 15: Durable responses achieved in a high-risk population
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Durable responses achieved in a high-risk population Cytogenetics Prior CA-4948 Best Molecular Dx ELN or Lines Prior Tx Duration Response Mutations IPSS-R3 Tx (#) (months) to CA-4948 ASXL1, NF1, PHF6, t-hrMDS1 Intermediate 1 azacitidine 6 Marrow CR • Respo
Slide 16: Signs of hematologic improvement with marrow blast reduction
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Signs of hematologic improvement observed in patients achieving significant marrow blast reduction mCR 82% blast reduction (11 to 2) • Following reduction in marrow blasts, patients saw 1 prior lines of therapy signs of hematologic recovery SD 63% blast re
Slide 17: Genomic analyses suggest disease-modifying activity of CA-4948
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Genomic analyses suggest disease-modifying activity of CA-4948 NGS RNA-seq Patient DNA Sequencing Patient RNA Sequencing • Genomic analyses depicted are from samples of two patients • DNA sequencing demonstrates the reduction of variant allele frequency af
Slide 18: Summary
A Phase 1 Trial: CA-4948 (IRAK4) in AML/MDS Summary • Oral CA-4948 monotherapy is safe and well tolerated at 200 mg, 300 mg, and 400 mg BID • Dose proportional exposure with minimal or no accumulation with continuous BID administration • Clear anti-cancer activity in R/R AML and hrMDS patients - Thr