Slide 1: Corporate Presentation
Corporate Presentation January 2025
Slide 2: Cautionary note regarding forward looking statements and disclaimers
Cautionary note regarding forward looking statements and disclaimers 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),” “beli
Slide 3: Emavusertib is a novel, first-in-class inhibitor of IRAK4
Emavusertib is a novel, first-in-class inhibitor of IRAK4 Acceptable safety profile in • Being evaluated in Phase 1/2 clinical studies monotherapy & combination in NHL, AML, and Solid Tumors • Cash runway into mid-2025 Demonstrated synergy o Sufficient to meet anticipated with BTKi, HMA, BCL2i near
Slide 4: Broad Market Opportunity in NHL and AML
Broad Market Opportunity in NHL and AML Current Programs Potential Expansion Opportunities ABC- PCNSL FLT3m AML WM MCL MZL CLL/SLL DLBCL US Incidence per 100K 0.51 1.32 4.23 0.55 0.56 1.57 2.08 4.59 Newly Diagnosed Per Year Newly Diagnosed Per Year US 1,7001 6,0002 20,0003 1,7005 1,7006 5,0007 6,800
Slide 5: Emavusertib in NHL
Emavusertib in NHL fen CUS’
Slide 6: Emavusertib's Mechanism in NHL
Emavusertib’s Mechanism in NHL BCR Pathway TLR Pathway 2 pathways drive NF-ĸB (which drives NHL) B cell TLR1 TLR2 TLR4 TLR5 receptor TLR6 blocking both pathways Endosome TLR7 TLR8 TLR9 (block BCR with BTKi – block TLR with emavusertib) ibrutinib (BTKi) BTK enables dual blockade of NF-ĸB Myddosome CA
Slide 7: Emavusertib synergy with BTKi demonstrated in NHL
Emavusertib synergy with BTKi demonstrated in NHL emavusertib + BTKi Monotherapy vs. Combination 1400 in NHL dual blockade of the TLR and BCR pathways 1200 vehicle was demonstrated to be more effective Mean Tumor Volume (mm3) + SEM 1000 than blocking either one alone 800 ibrutinib (BTKi) emavusertib
Slide 8: Strategy in NHL
Strategy in NHL ❶ Demonstrate safety 31 patients1 treated in TakeAim Lymphoma Ph 1b study, acceptable safety profile established, no overlapping dose-limiting toxicity with ibrutinib ❷ Demonstrate single-agent activity Single-agent activity demonstrated, with patients remaining on study up to 4 year
Slide 9: Emavusertib safety profile in NHL
Emavusertib safety profile in NHL1 • 31 patients treated with emavusertib in 100 mg BID 200 mg BID 300 mg BID Total combination with ibrutinib in multiple NHL subtypes Grade 3+ TRAE ema +ibr ema +ibr ema +ibr (n=31) in > 1 Patient (n=6) (n=18) (n=7) • Shown to be well tolerated with an acceptable n
Slide 10: Strategy in NHL
Strategy in NHL ❶ Demonstrate safety 31 patients1 treated in TakeAim Lymphoma Ph 1b study, acceptable safety profile established, no overlapping dose-limiting toxicity with ibrutinib ❷ Demonstrate single-agent activity Single-agent activity demonstrated, with patients remaining on study up to 4 year
Slide 11: Single-agent activity demonstrated in NHL
Single-agent activity demonstrated in NHL Tumor Reduction Sustained up to 3+ years Case Study in Dose Response (WM patient) 50 mg 100 mg 2950 2850 2750 200 mg 2650 2550 Dosing increases 2450 led to deeper response 2350 2250 2150 2050 1950 IgM (mg/dL) 1850 1750 300 mg 1650 1550 1450 1350 1250 1150 10
Slide 12: Strategy in NHL
Strategy in NHL ❶ Demonstrate safety 31 patients1 treated in TakeAim Lymphoma Ph 1b study, acceptable safety profile established, no overlapping dose-limiting toxicity with ibrutinib ❷ Demonstrate single-agent activity Single-agent activity demonstrated, with patients remaining on study up to 4 year
Slide 13: BTKi is currently used in 6 NHL subtypes
BTKi is currently used in 6 NHL subtypes PCNSL was selected as our first NHL indication for pursuing FDA approval Tumor Incidence in U.S. Key Targets of Interest Therapies Used ABC-DLBCL 2 per 100,000 ~ 6,800 patients IRAK4, MYD88, CD79, NF-kB R-CHOP, BTKi PCNSL 0.5 per 100,000 ~ 1,700 patients IRAK
Slide 14: Treatment lines in PCNSL
Treatment lines in PCNSL Critical unmet need – patients often proceed to hospice after 2 lines of treatment Salvage Line Stay on BTKi – add emavusertib emavusertib 1st Line 2nd Line + blocking both the TLR and BCR pathways BTKi maximizes downregulation of NF-κB and (ibrutinib) may lead to tumor redu
Slide 15: Encouraging clinical data in R/R PCNSL
Encouraging clinical data in R/R PCNSL Results for patients treated with emavusertib + ibrutinib, after they have progressed on prior BTKi 10% * Tumor Reduction Duration of Treatment 0% -10% Best change in disease burden from baseline -20% -30% 6 Responses Duration of Response > 6 months -40% in 10
Slide 16: PCNSL Case Study
PCNSL Case Study Patient with R/R PCNSL treated with emavusertib + ibrutinib Male patient, 53 yrs Diagnosis: PCNSL diagnosed on 30 Jun 2020 Baseline: Depression, elevated LFTs, loss of appetite, cerebral edema, mixed IBS, hiatal hernia, GERD, essential hypertension, and obstructive sleep apnea Prior
Slide 17: PCNSL Case Study
PCNSL Case Study Patient with R/R PCNSL who achieved CR on emavusertib + ibrutinib Relapsed on ibrutinib SD CR CR CR CR Nov 2022 Jan 2023 Apr 2023 May 2023 Aug 2023 Feb 2024 May 2024 (Screening) (Day 43) (Day 81) (Day 187) (Day 349) (Day 442) Tumor Size Disease Stable Tumor Absent Tumor Absent Tumor
Slide 18: Strategy in NHL
Strategy in NHL ❶ Demonstrate safety 31 patients1 treated in TakeAim Lymphoma Ph 1b study, acceptable safety profile established, no overlapping dose-limiting toxicity with ibrutinib ❷ Demonstrate single-agent activity Single-agent activity demonstrated, with patients remaining on study up to 4 year
Slide 19: Anti-cancer activity shown across multiple NHL subtypes
Anti-cancer activity shown across multiple NHL subtypes Data presented at ASH 2023 supports emavusertib + BTKi combination in additional NHL subtypes All patients (n=19), multiple NHL subtypes No Prior BTKi Failed Prior BTKi • Heavily pre-treated patients Best % Change in Tumor Burden (1-10 prior li
Slide 20: Summary in NHL
Summary in NHL Lymphoma • Emavusertib has demonstrated anti-cancer activity in R/R PCNSL • Received Orphan Drug designation in EMA • Next steps: ⁻ Work with FDA and EMA to align on a registrational path in R/R PCNSL ⁻ Prioritize additional NHL indications (after PCNSL) that could benefit from the du
Slide 21: Emavusertib in AML
Emavusertib in AML fen CUS’
Slide 22: Emavusertib binds to IRAK4 and FLT3, blocking both the TLR and FLT3 pathways
Emavusertib binds to IRAK4 and FLT3, blocking both the TLR and FLT3 pathways Emavusertib Emavusertib Kinase Interaction Map Binding Affinity FLT3 Target Kd nM IRAK4 IRAK1 12,000 IRAK2 >20,000 IRAK3 8,500 IRAK4 DYRK1A 23 25 Binds tightly to IRAK4 CLK 1, 2, 4 FLT3 WT 31 Haspin FLT3 (D835H) FLT3 (D835V
Slide 23: IRAK4-L is an independent and powerful driver of disease in AML
IRAK4-L is an independent and powerful driver of disease in AML IRAK4-L is expressed in nearly all AML patients IRAK4-L is oncogenic in AML 800 Knocking out IRAK4 IRAK4-L stops leukemic activity IRAK4-S (similar findings using CRISPR/CAS9) 600 Sum of IRAK4 variants Control 400 200 adding back IRAK4-
Slide 24: Strategy in AML
Strategy in AML ❶ Demonstrate safety 102 AML patients1 treated in TakeAim Leukemia Ph 1/2 study, acceptable safety profile established ❷ Demonstrate single-agent activity Single-agent activity observed; next step is to confirm these initial findings in a larger number of patients ❸ Pursue fastest pa
Slide 25: Grade ≥3 Treatment-Related Adverse Events in All Treated R/R AML Patients
Grade ≥ 3 Treatment-Related Adverse Events (TRAEs) in All Treated R/R AML Patients Emavusertib has an acceptable and manageable safety profile in R/R AML patients Source: TakeAim Leukemia FLT3 Clinical Presentation ASH 2024. Data as of October 31, 2024 * Three events of rhabdomyolysis were investiga
Slide 26: Strategy in AML
Strategy in AML ❶ Demonstrate safety 102 AML patients1 treated in TakeAim Leukemia Ph 1/2 study, acceptable safety profile established ❷ Demonstrate single-agent activity Single-agent activity observed; next step is to confirm these initial findings in a larger number of patients ❸ Pursue fastest pa
Slide 27: Single-agent activity demonstrated in AML
Single-agent activity demonstrated in AML Patients with < 3 lines of prior therapy with All Patients, All Dose Levels FLT3 mutation and treated at 300mg BID 100% 100% 80% 80% 60% 60% 40% Before enriching 40% 10 of 19 evaluable patients for Optimal Dose & FLT3m achieved objective response1 20% 20% En
Slide 28: Strategy in AML
Strategy in AML ❶ Demonstrate safety 102 AML patients1 treated in TakeAim Leukemia Ph 1/2 study, acceptable safety profile established ❷ Demonstrate single-agent activity Single-agent activity observed; next step is to confirm these initial findings in a larger number of patients ❸ Pursue fastest pa
Slide 29: Emavusertib in FLT3m AML
Emavusertib in FLT3m AML fen CUS’
Slide 30: Emavusertib's dual-targeting of IRAK4 and FLT3 enables monotherapy opportunity in FLT3m AML
Emavusertib’s dual-targeting of IRAK4 and FLT3 enables monotherapy opportunity in FLT3m AML IRAKi synergy with FLT3i 100% – 75% – FLT3i Control IRAK4 inhibition overcomes adaptive resistance to FLT3i 50% – IRAKi 25% – Concomitant targeting of IRAK1 or IRAK4, alongside FLT3, is the most effective mea
Slide 31: Treatment lines in AML with FLT3m
Treatment lines in AML with FLT3m Critical unmet need – patients with FLT3m develop resistance to current FLT3i therapies 1st Line Chemo Fit Patients FLT3i Relapsed/Refractory Salvage Line midostaurin quizartinib FLT3i gilteritinib emavusertib HMA Unfit Patients venetoclax Enroll patients after they
Slide 32: Emavusertib is a potential best-in-class therapy in FLT3m AML
Emavusertib is a potential best-in-class therapy in FLT3m AML CR + CRh/i Rate Salvage Line 40% emavusertib is 38% 35% CRh/i 9.5% 81% of patients 30% were previously treated with a FLT3i (n=21) FLT3i-naïve 25% Benchmark is 21% 20% CRh 13% of patients 15% 9.4% CR were previously treated with a FLT3i 2
Slide 33: Encouraging updated data in FLT3m AML
Encouraging updated data in FLT3m AML presented at ASH 2024 200 mg BID (n=3) Duration of Treatment MLFS CR CRi CR MLFS CR MLFS MLFS 7 of 10 responders achieved their first response at first assessment CRi Proceeded to stem cell transplant CRh (Cycle 2 Day 1) Patient MLFS CR Proceeded to stem cell tr
Slide 34: Strategy in AML
Strategy in AML ❶ Demonstrate safety 102 AML patients1 treated in TakeAim Leukemia Ph 1/2 study, acceptable safety profile established ❷ Demonstrate single-agent activity Single-agent activity observed; next step is to confirm these initial findings in a larger number of patients ❸ Pursue fastest pa
Slide 35: Emavusertib in All Comers
Emavusertib in All Comers fen CUS’
Slide 36: Emavusertib combination with aza/ven targets all comers in frontline AML
Emavusertib combination with aza/ven targets all comers in frontline AML oncogenic IRAK4-L is expressed emavusertib synergy with aza/ven ema/aza/ven in nearly all AML patients in preclinical studies triplet combination 800 Preclinical Data All Comers Model Relative cell growth in AML cell lines (THP
Slide 37: Summary in AML
Summary in AML Leukemia • Emavusertib targets both FLT3 and IRAK4 • Emavusertib offers potential for best-in-class therapeutic in FLT3m AML (a genetically-defined population) • Oncogenic IRAK4 is expressed in nearly all AML patients and is not addressed by current standard-of-care (azacitidine and v
Slide 38: Solid Tumors
Solid Tumors fen CUS’
Slide 39: Ongoing studies (ISTs) of emavusertib in Solid Tumors
Ongoing studies (ISTs) of emavusertib in Solid Tumors Tumor Type Institution (Investigator) Emavusertib Combination Partner Pancreatic CRADA Washington University (Grierson, Lim) gemcitabine, nab-paclitaxel CRADA Oklahoma University (Ulahannan) Colorectal FOLFOX, bevacizumab Washington University (L
Slide 40: Other Information
Other Information fen CUS’
Slide 41: Financials and IP
Financials and IP We believe cash is sufficient to achieve As of September 30, 20241 anticipated near-term milestones $31.6M Cash and Investments • Updated PCNSL data in ~20 patients (1Q25) ~8.5M Shares Outstanding • AML triplet initial safety data (1Q25) ~12.0M Shares Fully Diluted 2035 Composition
Slide 42: End of Presentation
End of Presentation fen CUS’