Curis, Inc. · NASDAQ:CRIS
Curis — Investor Presentation (September 2022)
50 slides from Curis's investor presentation, September 2022
Slide 1: Corporate Presentation
Corporate Presentation NASDAQ: CRIS
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: Corporate Overview
Corporate Overview Summary Curis develops novel, first-in-class, cancer therapeutics Investment in areas of significant unmet patient need Thesis Cash runway into 2024 – $107M as of June 30, 2022 First-in-Class Emavusertib: first-in-class oncology program targeting IRAK4 Pipeline CI-8993: first-in-c
Slide 4: Pipeline
Pipeline Curis develops novel, first-in-class cancer drugs PRE-CLINICAL CLINICAL MARKETED Dose Clinical Indication Proof of Principle Safety Optimization Activity Pivotal Commercial Two programs Heme Malignancies are the focus of this presentation emavusertib* IRAK4-driven Leukemia IRAK4 (AML/MDS) T
Slide 5: IRAK4 Biology and Emavusertib
IRAK4 Biology and Emavusertib
Slide 6: IRAK4 Biology and Emavusertib
IRAK4 Biology and Emavusertib IRAK4 is a novel and important target across multiple heme malignancies IRAK4 in AML/MDS IRAK4 in NHL/CLL Spliceosome mutation drives overexpression of IRAK4-L TLR Pathway is dependent upon IRAK4 for function (which causes constitutive activation of the myddosome) (2nd
Slide 7: Emavusertib's Unique Molecular Fingerprint
Emavusertib’s Unique Molecular Fingerprint The NCI has selected emavusertib Targeted design specifically engineered to hit key oncogenic targets for both clinical and non-clinical studies of IRAK4 inhibition Emavusertib Emavusertib in oncology Kinase Interaction Map Binding Affinity Target Kd nM NCI
Slide 8: Emavusertib Preclinical Data
Emavusertib Preclinical Data Clear anti-cancer activity suggests broad potential across heme malignancies AML/MDS B Cell Cancers Monotherapy Combination Therapy Combination Therapy 100% vehicle p<0.05 1200 Vehicle Mean Tumor Volume (mm3) ± SEM Relative Cell Growth p<0.05 900 50% ibrutinib p<0.05 ema
Slide 9: Emavusertib in Lymphoma (NHL/CLL)
Emavusertib in Lymphoma (NHL/CLL)
Slide 10: Emavusertib in B Cell Cancers
Emavusertib in B Cell Cancers Combination therapy provides complimentary inhibition of two pathways that drive NF-κB Two Pathways Drive B Cell Cancers Clinical Strategy: Use Combination Therapy BCR and TLR Pathways independently drive NF-κB overactivity In preclinical testing, blocking both IRAK4 an
Slide 11: Responses Seen in Both BTK-Naïve and BTK-Experienced Patients
Responses Seen in Both BTK-Naïve and BTK-Experienced Patients Majority of patients achieved decreases in tumor burden 20% Best Response 100% Change in Tumor Burden Over Time SD * Best % Change in Tumor Burden from Baseline 80% BTK-Naïve BTK-Experienced % Change in Tumor Burden from Baseline 0% 60% 4
Slide 12: Emavusertib in Lymphoma (NHL/CLL)
Emavusertib in Lymphoma (NHL/CLL) The ideal candidate to combine with BTKi to maximize downregulation of NF-κB • Patients are treated with BTKi because it downregulates NF-κB • Two pathways drive NF-κB: Next Steps 1) BCR Pathway: addressed by blocking BTK TakeAim Lymphoma Study 2) TLR Pathway: addre
Slide 13: Emavusertib in Leukemia (AML/MDS)
Emavusertib in Leukemia (AML/MDS)
Slide 14: Emavusertib in AML/MDS
Emavusertib in AML/MDS Clinical studies designed to leverage the role of IRAK4 and FLT3 in AML/MDS % of Patient Disease Driver Population Rationale for Monotherapy IRAK4-L > 50%1 • IRAK4 is the most prevalent genetic target in AML/MDS1,2 FLT3 > 25%2 • IRAK4 signaling is the adaptive response mechani
Slide 15: Encouraging Clinical Activity in R/R AML/MDS
Encouraging Clinical Activity in R/R AML/MDS Monotherapy activity in patients with Spliceosome and FLT3 mutations Best Response Efficacy Population #1: AML Spliceosome Patients1 CR/CRh Rate 2/5 (40%) The CR and CRh patients CR 1/5 (20%) are both MRD-negative CRh 1/5 (20%) Population #2: MDS Spliceos
Slide 16: Initial Emavusertib Data Compare Favorably to Existing Therapies
Initial Emavusertib Data Compare Favorably to Existing Therapies Potential to meaningfully improve outcomes in R/R AML patients with spliceosome mutation Most Commonly Used Therapies in R/R AML Patients without FLT3 Mutation1 Emavusertib Decitabine2,3 Azacitidine2,4 LoDAC5 patients achieving CR/CRh
Slide 17: Clear Unmet Need in Relapsed/Refractory MDS
Clear Unmet Need in Relapsed/Refractory MDS Current standard of care offers little therapeutic benefit to patients Most Commonly Used Therapies in R/R MDS1 Emavusertib Chemotherapy2 Decitabine3 Azacitidine3 IRAK4 Inhibitor Chemotherapy HMA HMA • ~8% ORR • 2nd line response data • 2nd line response d
Slide 18: Emavusertib May Address Unmet Need in R/R AML Patients with FLT3 Mut
Emavusertib May Address Unmet Need in R/R AML Patients with FLT3 Mut No approved therapies for patients R/R to FLT3 inhibitors Most Commonly Used Therapies in R/R AML Patients with FLT3 Mutation1 Emavusertib Gilteritinib2,3 Azacitidine2 Decitabine2 IRAK4 Inhibitor FLT3 Inhibitor HMA HMA • 33% CR • ~
Slide 19: Emavusertib in Leukemia (AML/MDS)
Emavusertib in Leukemia (AML/MDS) The ideal candidate to address the two largest genetic populations in AML/MDS Emavusertib addresses the two largest genetic populations in AML/MDS: 1 1) IRAK4 (>50% of population) 2 2) FLT3 (>25% of population) Next Steps • Clear single-agent activity TakeAim Leukem
Slide 20: VISTA Biology and CI-8993
r~ CURIS = VISTA Biology and Cl-8993
Slide 21: CI-8993: Novel Checkpoint Inhibitor
CI-8993: Novel Checkpoint Inhibitor Published research suggests VISTA has a broad role among checkpoint inhibitors We believe VISTA inhibition has potential for broad application in many tumor types in monotherapy and in combination with existing checkpoint inhibitors Target Checkpoint Inhibitors Ap
Slide 22: CI-8993 Preclinical Data
CI-8993 Preclinical Data Clear single-agent activity; potential to transform immune-oncology treatment in combination Monotherapy Combination Therapy Anti-VISTA inhibited tumor growth Anti-VISTA inhibited xenograft growth in B16ova melanoma model1 in checkpoint resistant CT26 model2 Control n=14 100
Slide 23: CI-8993 Initial Clinical Data
CI-8993 Initial Clinical Data CI-8993 is demonstrating a favorable PK profile Plasma Concentration Cmax Levels 1,000,000 1,000,000 Mean 0.15 mpk DAY 1 (ng/mL) Concentration(ng/mL) Mean 0.15 mpk DAY 29 Mean 0.3 mpk DAY 1 100,000 100,000 Mean 0.3 mpk DAY 29 78.4-fold PlasmaConcentration Mean 0.6 mpk D
Slide 24: CI-8993 Initial Clinical Data
CI-8993 Initial Clinical Data Initial data show reduction of MDSCs entering tumor & increased NK cell activation Decreased recruitment of MDSCs NK Cell Activation 1 2 Decreased CXCR2 on granulocytes Decreased CD16 on NK cells CI-8993 reduces MDSCs Cohort 1 Cohort 2 Cohort 1 Cohort 2 CI-8993 activate
Slide 25: CI-8993 Initial Clinical Data
CI-8993 Initial Clinical Data Initial data show enhanced antigen presentation & increased T cell activation factors Enhanced Antigen Presentation Release of T-Cell Activating Factors 4 5 Increased HLA-DR on Monocytes Increased Secretion of IP10 CI-8993 enhances antigen Cohort 1 Cohort 2 Cohort 1 Coh
Slide 26: CI-8993 Encouraging Progress at Early Dose Levels
CI-8993 Encouraging Progress at Early Dose Levels First-in-class CI-8993 has potential for broad applicability in immune checkpoint therapy • Favorable PK profile Next Steps in Dose Escalation • Saturation kinetics (“sink effect”) appear to be addressed with increase in dose level • Looks for additi
Slide 27: Corporate Overview
Corporate Overview Summary Curis develops novel, first-in-class, cancer therapeutics Investment in areas of significant unmet patient need Thesis Cash runway into 2024 – $107M as of June 30, 2022 First-in-Class Emavusertib: first-in-class oncology program targeting IRAK4 Pipeline CI-8993: first-in-c
Slide 28: End of Corporate Presentation
End of Corporate Presentation NASDAQ: CRIS
Slide 29: Appendix
APPENDIX
Slide 30: Emavusertib PK/PD
Emavusertib PK/PD Attractive PK profile supports BID dosing and high target suppression Attractive PK Profile High Target Suppression • Half-life of ~6 hours Trough • Exposure at RP2D correlates with 98% inhibition Exposure Dose Inhibition • Supports BID dosing regimen 2.5μM 200mg 97% 4.1μM 300mg 98
Slide 31: Dose Response in Single Patient at Multiple Dose Levels
Dose Response in Single Patient at Multiple Dose Levels Patient in dose escalation phase of TakeAim Lymphoma study Dose Response Observed in WM Patient (50mg - 300mg BID) Clear Single Agent Anti-Cancer Activity • Tumor burden decreased with each increase in dose (objective response observed at RP2D)
Slide 32: Emavusertib Clinical Plan
Emavusertib Clinical Plan Ongoing clinical studies in AML/MDS and B cell cancers AML/MDS AML/MDS B Cell Cancers Monotherapy Combination Therapy Combination Therapy (relapsed/refractory) (relapsed/refractory) (relapsed/refractory) Patients Patients Patients with IRAK4 Pathway activation with Targeted
Slide 33: Emavusertib in B Cell Cancers
Emavusertib in B Cell Cancers
Slide 34: Emavusertib in B Cell Cancers
Emavusertib in B Cell Cancers Proof-of-Concept demonstrated with monotherapy; Combination therapy study in progress Monotherapy Combination Therapy Ph1 proof-of-concept study Blocking both IRAK4 and BTK demonstrated durable tumor reduction in monotherapy may be better than blocking either one alone
Slide 35: Emavusertib in AML/MDS
Emavusertib in AML/MDS
Slide 36: Emavusertib in AML and MDS
Emavusertib in AML and MDS TakeAim Leukemia Trial - Open-label, single arm, Phase 1/2 dose escalation and expansion study Dose Escalation: Dose Expansion: 200/300/400/500 mg BID 300 mg BID Study Objectives 1ᵒ: Determine maximum tolerated dose Determine recommended Phase 2 dose 2ᵒ: Pharmacokinetic (P
Slide 37: Safety Profile for emavusertib
Safety Profile for emavusertib 49 total patients with AML/MDS treated with emavusertib Recommended Phase 2 Dose 200 mg BID 300 mg BID 400 mg BID 500 mg BID Grade 3+ Treatment-Related Adverse Event (N = 3) (N = 26) (N = 17) (N = 3) n (%) n (%) n (%) n (%) Number of patients having grade 3+ treatment-
Slide 38: Clinical Data: R/R AML Patients with Spliceosome Mutation
Clinical Data: R/R AML Patients with Spliceosome Mutation Patient Population #1 38
Slide 39: Unmet Need for R/R AML Patients with Spliceosome Mutation
Unmet Need for R/R AML Patients with Spliceosome Mutation No approved targeted therapies and no unified standard of care for these patients Elderly / • Spliceosome mutations occur in ~10% of AML patients1 Intensive Non-Intensive Induction Ven/HMA - These mutations create a chronic inflammatory marro
Slide 40: 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 Prior Therapies Duration on Dose Baseline Molecular Blasts Blasts Best Dx Risk Category emavusertib % Change (BID) Mutations Baseline
Slide 41: Clinical Data: R/R MDS Patients with Spliceosome Mutation
Clinical Data: R/R MDS Patients with Spliceosome Mutation Patient Population #2 41
Slide 42: Spliceosome Mutations Common in MDS
Spliceosome Mutations Common in MDS Large unmet need for R/R MDS patients with spliceosome mutation • Spliceosome mutations (U2AF1/SF3B1) are the most prominent mutations in MDS, accounting for ~30% of all MDS patients1 SCT Eligible Not SCT Eligible HMA HMA - These mutations create a chronic inflamm
Slide 43: Encouraging Clinical Activity in R/R MDS Patients with Spliceosome Mutation
Encouraging Clinical Activity in R/R MDS Patients with Spliceosome Mutation Marrow blast reduction achieved in 5 of 7 patients, including 4 marrow CRs Prior Therapies Duration on Dose Baseline Molecular Blasts Blasts Best Dx IPSS-R emavusertib % Change (BID) Mutations # Baseline Response Therapy (mo
Slide 44: Clinical Data: R/R AML Patients with FLT3 Mutation
Clinical Data: R/R AML Patients with FLT3 Mutation Patient Population #3 44
Slide 45: Emavusertib in AML/MDS with FLT3 Mutation
Emavusertib in AML/MDS with FLT3 Mutation IRAK4 inhibition is synergistic with, and prevents adaptive resistance to, FLT3 inhibition IRAK Activity IRAK1/4i Synergy with FLT3i Leukemia-free Survival increases after treatment with FLT3i IRAK1/4i + FLT3i Combination vs FLT3i alone 100 – 100 – 0.8 – FLT
Slide 46: 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 emavusertib monotherapy Risk Prior Therapies Duration on Dose Baseline Molecular Blasts Blasts Best Dx Category emavusertib % Change (BID) Mutations Baseline Respon
Slide 47: VISTA Biology and CI-8993
r~ CURIS = VISTA Biology and Cl-8993
Slide 48: Incorporated Learnings from CI-8993 Prior Clinical Study
Incorporated Learnings from CI-8993 Prior Clinical Study Pharmacodynamic activity (cytokine release) observed in initial 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 • Tra
Slide 49: 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 Phase 1 Dose Escalation Study Design (includes mesothelioma, melanoma, NSCLC, TNBC) Treatment Higher Continue dose escalation • Bi-week
Slide 50: CI-8993 Has Demonstrated Favorable Safety Profile
CI-8993 Has Demonstrated Favorable Safety Profile Successfully managed expected CRS at all levels dosed to date All Grades 0.15 mg/kg 0.3 mg/kg Grade 3+ 0.15 mg/kg 0.3 mg/kg Treatment-Related Adverse Events (N = 7) (N = 5) Treatment-Related Adverse Events (N = 7) (N = 5) Occurring in 2+ Patients n (