Curis, Inc. · NASDAQ:CRIS
Curis — Technical Presentation (2020)
13 slides from Curis's technical presentation, 2020
Slide 1: Safety, Pharmacokinetics and Activity of CA-4948, an IRAK4 Inhibitor: Phase 1 Results
# 703: Safety, Pharmacokinetics and Activity of CA-4948, an IRAK4 Inhibitor For Treatment of Patients with Relapsed or Refractory Hematologic Malignancies: Results from the Phase 1 Study Grzegorz Nowakowski MD1, Lori A. Leslie MD2, Anas Younes, MD3, Erel Joffe, MD3, Allison Rosenthal, MD4, Krish Pat
Slide 2: Interleukin-1 Receptor-Associated Kinase-4 (IRAK4)
Interleukin-1 Receptor-Associated Kinase-4 (IRAK4) A novel target for addressing cancer through the TLR Pathway BTK and TLR are parallel pathways that drive oncogenic activity as primary independent activators of NF-κB BTK Pathway TLR Pathway B cell TLR1 TLR2 TLR4 TLR5 receptor TLR6 BTK Pathway is O
Slide 3: CA-4948: A Novel Small Molecule IRAK4 Kinase Inhibitor
CA-4948: A Novel Small Molecule IRAK4 Kinase Inhibitor IRAK4/CA-4948 Co-crystal Structure • First-in-class IRAK4 inhibitor in oncology • Very good oral bioavailability • ATP-competitive, type 1 reversible inhibitor • High binding affinity to IRAK4 (23 nM) and FLT3 • Inhibits hematological malignanci
Slide 4: In-Vivo Activity: Monotherapy and Combination Therapy in DLBCL Model
In-Vivo Activity Anti-Cancer Activity in Monotherapy and Combination Therapy in MYD88-altered DLBCL model (OCI-Ly10) 1500 vehicle 1200 Mean Tumor Volume 900 (mm3) ± SEM ibrutinib CA-4948 Monotherapy 600 300 Combination Therapy (CA-4948 + ibrutinib) 0 0 5 10 15 20 25 30 ibrutinib dosing 12.5mg/kg; Da
Slide 5: Trial Design
Trial Design Phase 1 dose escalation study Study Objectives in patients with relapsed/refractory (R/R) NHL Primary: Safety and tolerability, DLTs, MTD and RP2D Characteristics & Study Disposition Overall Secondary: Pharmacokinetic (PK) profile (N=31) Male, n (%) 26 (80) Preliminary anti-cancer activ
Slide 6: Treatment Emerging Adverse Events
Treatment Emerging Adverse Events As of the cut-off date, most AEs have been Grade 1-2, manageable, and reversible 200 mg BID 300 mg BID 400 mg BID All General (n=5); (%) (n=6); (%) (n=8); (%) (n=30); (%) Adverse Reaction • No Grade 5 toxicity All Grade All Grade All Grade All Grades 3 or 4 Grades 3
Slide 7: Clinical PK
Clinical PK DAY 1 CA-4948 Mean Plasma Concentration versus • CA-4948 is rapidly absorbed, with maximum plasma time Profile following BID Oral Administration concentrations observed 0.5 - 8.0 hours after dosing Mean 50mg BID Mean 100mg BID Mean CA-4948 Plasma Concentration (ng/mL) Mean 200mg BID • Ha
Slide 8: Dose Response in Single Patient at Multiple Dose Levels
Dose Response in Single Patient at Multiple Dose Levels Clear dose response observed Tumor burden reduced with each increase in dose 8
Slide 9: Tumor Response
Tumor Response NHL Initial Dose Final Dose Tumor Subtype Level Level Reduction DLBCL 50mg bid 50mg bid 11% DLBCL (t-MZL) 50mg qd 50mg qd 24% FL 50mg qd 50mg qd 35% FL 100mg qd 50mg qd 49% WM* 50mg bid 300mg bid 67% PR LPL* 200mg bid 300mg bid 20% DLBCL 200mg bid 300mg bid 35% WM 300mg bid 300mg bid
Slide 10: Treatment Duration
Treatment Duration • Acceptable safety and tolerability profile at RP2D, including 3 patients who have been on study 1-2 years • Long-term PR or stable disease translate into patient benefit
Slide 11: Predictive Biomarkers
Predictive Biomarkers Two Potential Predictive Biomarkers for CA-4948: Confirmation of 2nd Predictive Biomarker Positive NFκB phospho-p50 protein expression (previously identified) correlates with Lymphoma Shrinkage or Stable Disease NFκB phospho-p50 MYD88 NEGATIVE POSITIVE Positive expression indic
Slide 12: Conclusions
Conclusions CA-4948 is a novel oral IRAK4 inhibitor of the TLR/myddosome Pathway • Well absorbed; pharmacokinetics are predictable and support BID dosing • Well tolerated; safety profile allows long-term treatment and combination with other active drugs against NHL • Pharmacodynamic analyses demonst
Slide 13: Thank you
Thank you Thanks to the participating trial investigators, clinical staff, the patients and their families. Correspondence Curis, Inc. 128 Spring St. Ste 500, Bldg. C Lexington, MA 024221 Contact Information: Reinhard von Roemeling, MD. rvonroemeling@curis.com 13