Curis (CRIS) Corporate presentation summary

Emavusertib clinical and preclinical highlights

• Demonstrated dual inhibition of IRAK4 and FLT3, showing efficacy in both lymphoma and AML models, with proof-of-concept data in PCNSL and mFLT3 AML indicating higher response rates than current standards of care.

• In PCNSL, achieved 63% ORR in BTKi-naïve and 27% ORR in BTKi-experienced patients; in mFLT3 AML, achieved 38% CR/CRh, outperforming gilteritinib.

• Dual blockade of BCR and TLR pathways in NHL and CLL models provided deeper responses than BTKi alone, supporting the rationale for combination therapy.

• Preclinical and clinical data suggest emavusertib can overcome adaptive resistance mechanisms in both CLL and AML.

• Ongoing registrational and phase 2 studies in PCNSL, CLL, and AML aim to confirm these findings and expand indications.

Clinical study designs and outcomes

• TakeAim Lymphoma and CLL studies include dose escalation, single-arm, and randomized trials to support accelerated and full approvals, focusing on deeper and more durable responses.

• In PCNSL, combination with BTKi in BTKi-naïve patients showed 63% ORR versus 39% for BTKi alone; in salvage line, 27% ORR where no standard of care exists.

• CLL studies target patients in partial remission on BTKi, aiming for complete remission and time-limited oral therapy.

• AML studies compare emavusertib to gilteritinib, with 38% composite CR rate in mFLT3 AML versus 21% for gilteritinib.

• Safety profile across NHL and AML cohorts is well tolerated, with no dose-limiting myelosuppression or CNS toxicities observed.

Mechanism of action and scientific rationale

• Emavusertib targets IRAK4 in the TLR pathway and FLT3, addressing key drivers of resistance and disease progression in CLL, NHL, and AML.

• Dual inhibition strategy is supported by preclinical data showing superior efficacy over single-agent BTKi or FLT3i.

• IRAK4-L isoform is a disease driver in nearly all AML patients, and its inhibition is critical for overcoming resistance.

• MRD (minimal residual disease) is emerging as a regulatory endpoint in CLL, with emavusertib studies designed to achieve MRD negativity.