Ryvu Therapeutics (RVU) Study Update summary

Program overview and study design

• RVU120, a first-in-class, oral CDK8/19 inhibitor, is being evaluated in four ongoing Phase II trials targeting hematologic malignancies, including AML, high-risk and low-risk MDS, and myelofibrosis, both as monotherapy and in combination regimens.

• The studies include RIVER-52 (monotherapy in AML/HR-MDS), RIVER-81 (combination with venetoclax in refractory AML), POTAMI-61 (myelofibrosis), and REMARK (low-risk MDS).

• The development plan targets high unmet needs, focusing on genetically defined patient cohorts (NPM1, DNMT3A) and combination strategies, with adaptive study designs.

• Preclinical and Phase I data support efficacy in NPM1 and DNMT3A mutant AML, with mechanistic rationale from transcriptomic profiling and synergy with venetoclax and ruxolitinib.

• Enrollment and site activation have accelerated, with over 100 patients dosed and more than 100 sites activated across Europe and Canada, expected to reach 113 sites by year-end 2024.

Phase II study progress and enrollment

• All four Phase II studies are actively enrolling, with significant increases in patient numbers and site activations in Q4 2024.

• RIVER-52 and RIVER-81 have completed initial dose escalation and are progressing to expansion cohorts.

• POTAMI-61 and REMARK have initiated dosing, with first efficacy data expected in Q2 2025.

• Data from the first 10+ evaluable patients in key cohorts are anticipated in H1 2025.

• Enrollment rates are supported by a strong investigator network and operational team.

Preliminary efficacy and safety findings

• Early data show promising efficacy, including blast reduction and hematologic improvement, especially in NPM1 and DNMT3A mutant AML and MDS cohorts.

• In RIVER-81, one patient achieved complete remission in a venetoclax-refractory population, and another showed significant blast reduction.

• RVU120 demonstrates a favorable safety profile, with low rates of severe adverse events, no significant QTc prolongation, and no differentiation syndrome observed.

• Initial signals of efficacy are also seen in myelofibrosis and low-risk MDS, with evidence of bone marrow fibrosis reduction and transfusion independence.

• Data remain preliminary, with most patients recently enrolled and ongoing treatment; robust efficacy conclusions await further follow-up.