Curis (CRIS) Study update summary

Study Design and Patient Cohorts

• TakeAim Lymphoma is a multi-part study evaluating emavusertib plus BTKi in relapsed/refractory PCNSL, with completed dose escalation, ongoing single-arm (BTKi-experienced), and randomized (BTKi-naive) phases.

• Both BTKi-naive and BTKi-experienced cohorts are being studied, with updated data cutoffs and ongoing enrollment.

• The TakeAim CLL study is an open-label phase 2 trial of emavusertib plus zanubrutinib in CLL patients with measurable residual disease, with 11 sites open and 10 patients consented.

• Year-end guidance for initial CLL data is 5-10 patients, with results expected in December 2026.

Efficacy Results in PCNSL and CLL

• ORR in BTKi-naive PCNSL patients reached 86% (6/7), and 100% in evaluable patients (5/5); other data show 71% ORR in BTKi-naive and 26% in BTKi-experienced (10/39).

• BTKi-experienced PCNSL patients showed a consistent ORR of 26% (10/39), rising to 33% in evaluable patients (10/30), with some maintaining responses over two years.

• Response rates in these populations exceed historical BTKi monotherapy data (40%-70% in naive, near 0% in post-BTKI progression).

• Early CLL data suggest emavusertib plus BTKi may enable deeper responses, including complete responses or undetectable MRD.

Mechanism of Action and Preclinical Validation

• Emavusertib is a dual IRAK4-FLT3 inhibitor targeting TLR/IRAK4 and BCR pathways, providing deeper responses and overcoming resistance in NHL, CLL, and AML.

• Preclinical data show dual blockade with emavusertib and BTKi is more potent than single agents in CLL and NHL models.

• The combination benefits patients with Cys481 or MYD88 mutations, common in PCNSL.