Slide 1: CA-4948 & CI-8993 Clinical Data Update
CA-4948 & CI-8993 Clinical Data Update January 2022 Exhibit 99.1
Slide 2: Cautionary Note Regarding Forward Looking Statements
Cautionary Note Regarding Forward Looking Statements This presentation contains certain forward-looking statements about Curis, Inc. (“we,” “us,” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Words such as “expect(s),” “believe(s),” “will,”
Slide 3: Today's Participants
Today’s Participants James Dentzer President & Chief Executive Officer at Curis Robert Martell, MD, PhD Head of R&D at Curis Daniel DeAngelo, MD, PhDChief, Division of Leukemia at Dana-Farber Cancer Institute
Slide 4: Introductory Remarks
Introductory Remarks Clinical update on CA-4948 (IRAK4) and CI-8993 (VISTA) CA-4948 addresses a novel target (IRAK4) and: (1) demonstrates clear anti-cancer activity as an oral single agent (2) is active in genetically-defined populations that can be identified and enrolled (3) has the added potenti
Slide 5: CA-4948: First-in-class IRAK4 Inhibitor Targeting Specific Genetic Populations
CA-4948: First-in-class IRAK4 Inhibitor Targeting Specific Genetic Populations in R/R AML and high-risk MDS (MDS)
Slide 6: Biology and CA-4948
Biology and CA-4948 Role of IRAK4 in AML/MDS (normal vs. oncogenic activity) 1. Smith et al. Nat Cell Biol 2019. 2. Guillamot et al. Nat Cell Biol 2019. constitutive activation MYD88 IRAK1 IRAK4-S Myddosome IRAK1 IRAK4-L MYD88 Malignant Heme Cell2 Spliceosome Spliceosome Normal Heme Cell1 Spliceosom
Slide 7: CA-4948 is the Leading IRAK4 Inhibitor in Development for Cancer
CA-4948 is the Leading IRAK4 Inhibitor in Development for Cancer Targeted design offers added potential benefit of also hitting FLT3 CA-4948 Kinase Interaction Map % Inhibition at 0.1 nM Illustration reproduced courtesy of Cell Signaling Technology CA-4948 binds specifically and with high affinity t
Slide 8: Clinical Study Overview
Clinical Study Overview Phase 1/2 Study in AML and MDS
Slide 9: CA-4948 in AML and MDS Study Objectives
CA-4948 in AML and MDS Study Objectives 1ᵒ: Determine maximum tolerated dose Determine recommended Phase 2 dose 2ᵒ:Pharmacokinetic (PK) profile Preliminary anti-cancer activity Study Population Relapsed/Refractory AML or high-risk MDS ECOG performance Status of ≤ 2 Age ≥ 18 years Dosing Oral, Twice
Slide 10: Well-Tolerated and Manageable AE Profile for CA-4948
Well-Tolerated and Manageable AE Profile for CA-4948 in AML/MDS with No Cumulative Toxicities Observed No Grade 4 or 5 TRAEs reported; all AEs were manageable Data extraction date: Dec 16, 2021. 1. Data for the two patients that have escalated from 300 mg BID to 400 mg BID were included in the 400 m
Slide 11: Clinical Data Overview: Three Targeted Patient Populations
Clinical Data Overview: Three Targeted Patient Populations (1) AML Spliceosome, (2) MDS Spliceosome, (3) AML FLT3
Slide 12: Heavily Pretreated Patient Population
Heavily Pretreated Patient Population Baseline Characteristics of AML/MDS Subsets AML Spliceosome1 (n=6) MDS Spliceosome (n=7) AML FLT31 (n=3) Female n (%) : Male n (%) 0 (0) : 6 (100) 5 (71) : 2 (29) 0 (0) : 3 (100) Age (yrs): median (range) 76 (60, 84) 74 (61, 80) 80 (78, 87) ECOG: n 0/1/2 0/4/2 2
Slide 13: Encouraging Clinical Activity in R/R AML/MDS Patient Populations
Encouraging Clinical Activity in R/R AML/MDS Patient Populations CA-4948 shows activity as a monotherapy in patients with Spliceosome and FLT3 mutations Population #1: AML Spliceosome Patients1 CR/CRh Rate 2/5(40%) CR 1/5(20%) CRh 1/5(20%) Population #2: MDS Spliceosome Patients Objective Response R
Slide 14: Clinical Data: R/R AML Patients with Spliceosome Mutation
Clinical Data: R/R AML Patients with Spliceosome Mutation Patient Population #1
Slide 15: Unmet Need for R/R AML Patients with Spliceosome Mutation
Unmet Need for R/R AML Patients with Spliceosome Mutation Spliceosome mutations occur in ~10% of AML patients1 These mutations create a chronic inflammatory marrow microenvironment2, which impairs hematologic recovery3 Ability to achieve CR is impaired in patients with U2AF1/SF3B1 mutation4 There ar
Slide 16: Initial CA-4948 Data Compare Favorably to Existing Therapies
Initial CA-4948 Data Compare Favorably to Existing Therapies Potential to meaningfully improve outcomes in R/R AML patients with spliceosome mutation 1. CancerMPact Treatment Architecture U.S. AML, Cerner Enviza, www.cancermpact.com, accessed January 3, 2022. Excludes Investigational Therapies; 2. P
Slide 17: Encouraging Clinical Activity in R/R AML Patients with Spliceosome Mutation
Encouraging Clinical Activity in R/R AML Patients with Spliceosome Mutation Achieved 40% CR/CRh rate, with treatment duration >6 months to date in responding patients CA-4948 achieved CR/CRh responses, despite transformed AML being historically highly resistant to treatment CR CRh Dx Dose (BID) Risk
Slide 18: Clinical Data: R/R MDS Patients with Spliceosome Mutation
Clinical Data: R/R MDS Patients with Spliceosome Mutation Patient Population #2
Slide 19: Spliceosome Mutations Common in MDS
Spliceosome Mutations Common in MDS Spliceosome mutations (U2AF1/SF3B1) are the most prominent mutations in MDS, accounting for ~30% of all MDS patients1 These mutations create a chronic inflammatory marrow microenvironment2, which impairs hematologic recovery3 There are no effective therapies for p
Slide 20: Clear Unmet Need in Relapsed/Refractory MDS
Clear Unmet Need in Relapsed/Refractory MDS Current standard of care offers little therapeutic benefit to patients 1. CancerMPact Treatment Architecture U.S. AML, Cerner Enviza, www.cancermpact.com, accessed January 3, 2022. Excludes Investigational Therapies; 2. Prébet et al, JCO 2011.; 3. Product
Slide 21: R/R MDS Patients with Spliceosome Mutation Response Data
Dx Dose (BID) IPSS-R Baseline Molecular Mutations Prior Therapies Duration on CA-4948 (mos) Blasts Baseline Blasts Best Response % Change # Lines Therapy MDS 200 mg Very High Risk U2AF1 ,ASXL1, NF1, PHF6, GFI1, KDM6A, TET2 1 azacitidine 5.7 11 2 -82% (mCR) MDS 300 mg Very High Risk U2AF1, DNMT3A, BC
Slide 22: Clinical Data: R/R AML Patients with FLT3 Mutation
Clinical Data: R/R AML Patients with FLT3 Mutation Patient Population #3
Slide 23: IRAK4 Signaling Drives Resistance to FLT3 Inhibitors
IRAK4 Signaling Drives Resistance to FLT3 Inhibitors IRAK4 inhibition is synergistic with, and prevents adaptive resistance to, FLT3 inhibition IRAK4 activity increases after quizartinib treatment of MLL-AF9 FLT3-ITD cells IRAK4 activity also shown to increase in patients during gilteritinib treatme
Slide 24: CA-4948 May Address Unmet Need in R/R AML Patients with FLT3 Mutation
CA-4948 May Address Unmet Need in R/R AML Patients with FLT3 Mutation No approved therapies for patients R/R to FLT3 inhibitors 1. CancerMPact Treatment Architecture U.S. AML, Cerner Enviza, www.cancermpact.com, accessed January 3, 2022. Excludes Investigational Therapies; 2. Product Package Insert;
Slide 25: Encouraging Clinical Activity in R/R AML Patients with FLT3 Mutation
Encouraging Clinical Activity in R/R AML Patients with FLT3 Mutation Achieving disease modification in heavily pretreated patients with CA-4948 monotherapy Significant marrow blast reduction and FLT3 mutation eradicated in 2 out of 3 patients Data extraction date: Dec 16, 2021; “+” in Duration of Tr
Slide 26: Summary CA-4948 in Three Targeted Patient Populations
Summary CA-4948 in Three Targeted Patient Populations
Slide 27: Comments from Clinical Investigator, Daniel DeAngelo, MD, PhD
Comments from Clinical Investigator, Daniel DeAngelo, MD, PhD Encouraging clinical activity in patients with R/R disease, all of whom had prior HMA treatment 4 out of 5 patients with spliceosome-mutated AML achieved blast reduction 2 patients achieved CR/CRh with significant hematologic improvement,
Slide 28: CA-4948 Has Potential to Address Clear Unmet Need in AML and MDS
CA-4948 Has Potential to Address Clear Unmet Need in AML and MDS First-in-class IRAK4 inhibitor targets specific genetic populations in AML and MDS Next Steps in Expansion Monotherapy: Spliceosome mutation Monotherapy: FLT3 mutation Combination: CA-4948 + azacitidine Combination: CA-4948 + venetocla
Slide 29: CI-8993: First-in-class VISTA Antagonist
CI-8993: First-in-class VISTA Antagonist Novel Immune Checkpoint Inhibitor for Solid Tumors
Slide 30: Anti-cancer Mechanisms of Checkpoint Inhibitors
Anti-cancer Mechanisms of Checkpoint Inhibitors Role of VISTA may go beyond other checkpoint inhibitors Target VISTA (CI-8993) þ þ þ þ þ PD-1 (Pembro, Nivo, etc.) þ ý ý ý þ PD-L1 (Atezo, Durva, etc.) ý ý ý ý þ CTLA-4 (Ipi) ý ý ý ý þ TIM3 þ ý ý ý þ LAG3 ý ý ý ý þ OX40 ý ý ý ý þ TIGIT ý ý ý ý þ We bel
Slide 31: Incorporated Learnings from CI-8993 Prior Clinical Study
Incorporated Learnings from CI-8993 Prior Clinical Study CI-8993 is the first anti-VISTA monoclonal antibody (IgG1κ) to be studied in clinical trials Janssen initiated a Ph1 study in 2016 and enrolled 12 patients1 Transient Cytokine Release Syndrome (CRS) observed in several patients at 0.15mg/kg Tr
Slide 32: CI-8993 Clinical Plan: Phase 1 Dose Escalation Study
CI-8993 Clinical Plan: Phase 1 Dose Escalation Study On-going clinical study to determine safety Patient Population Patients with advanced refractory solid tumors (includes mesothelioma, melanoma, NSCLC, TNBC) Treatment Bi-weekly dosing Plan to mitigate potential toxicities by co-medication and step
Slide 33: CI-8993 Has Demonstrated Favorable Safety Profile
CI-8993 Has Demonstrated Favorable Safety Profile Successfully managed expected CRS at all levels dosed to date Data extraction date: Dec 11, 2021. One additional patient experienced grade 2 treatment-related AE after receiving step dose and chose not to proceed to full dose. CI-8993 has successfull
Slide 34: CI-8993 Has Demonstrated Favorable PK Profile
CI-8993 Has Demonstrated Favorable PK Profile CI-8993 mean plasma concentration vs. time profile following IV administration at full dose 3.5-fold 1.5-fold 9.8-fold 8.0-fold 78.4-fold Cmax Levels Log-Mean ± SE CI-8993 Plasma Concentration (ng/mL) 100,000 1,000,000 10,000 1,000 100 10 1 Saturation ki
Slide 35: Pharmacodynamic Effects of CI-8993 in Patients
Pharmacodynamic Effects of CI-8993 in Patients CI-8993 affects multiple anticancer mechanisms supporting VISTA potential Decreased recruitment of MDSCs Decreased CXCR2 on granulocytes 1 2 NK Cell Activation Decreased CD16 on NK cells Baseline Pre-1st Dose Post-1st Dose Pre-3rd Dose Baseline Pre-1st
Slide 36: Pharmacodynamic Effects of CI-8993 in Patients
Pharmacodynamic Effects of CI-8993 in Patients CI-8993 affects multiple anticancer mechanisms supporting VISTA potential Enhanced Antigen Presentation Increased HLA-DR on Monocytes 4 5 Release of T-Cell Activating Factors Increased Secretion of IP10 Similar finding for MIP1a Baseline Pre-1st Dose Po
Slide 37: CI-8993 Cleared Initial Safety Hurdle
CI-8993 Cleared Initial Safety Hurdle First-in-class CI-8993 has potential for broad applicability in immune checkpoint therapy Encouraging initial safety data appears to demonstrate effectiveness of procedures implemented to manage expected CRS Pharmacokinetic profile of CI-8993 exhibits saturation
Slide 38: Closing Comments
Closing Comments
Slide 39: Closing Remarks & Next Steps
Initial clinical data demonstrate clear anti-cancer activity with a single, oral agent in specific genetic populations of AML/MDS Initial safety data appear to demonstrate that expected immune effects (cytokine release) can be managed, and early PK/PD data show that anti-cancer mechanisms are being
Slide 40: Q&A
Q&A