Ryvu Therapeutics (RVU) Study Update summary

Program overview and study design

• RVU120, a selective oral CDK8/19 inhibitor, is being evaluated in four ongoing Phase II trials targeting 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), with adaptive designs focusing on genetically defined cohorts.

• Enrollment and site activation have accelerated, with over 100 sites activated across Europe and North America and nearly 100 patients dosed by year-end 2024.

• The program targets high unmet needs, leveraging preclinical and Phase I data supporting efficacy in NPM1 and DNMT3A mutant AML and showing synergy with venetoclax and ruxolitinib.

• The program is fully funded through Q1 2026, with all studies progressing on budget.

Preliminary efficacy and safety findings

• Early data show promising efficacy, including a 50% blast reduction in NPM1-mutated AML, disease stabilization in DNMT3A-mutated patients, and a complete remission in venetoclax-refractory AML.

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

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

• Target engagement of 50-70% at 250 mg dose supports robust antileukemic activity.

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

Operational progress and future outlook

• Enrollment rates and site activations have increased significantly, supported by a strong investigator network and global clinical footprint.

• Commercial opportunities are substantial, with potential markets in AML, MDS, and myelofibrosis valued at several hundred million to over $1.2B in front-line AML alone.

• Expansion into new geographies, including the U.S., is planned as studies progress.

• All studies are progressing within budget, with a planned program review in H1 2025 to focus on the most promising development paths.

• Next major data updates are expected in Q1 and Q2 2025, with the potential for accelerated or regular approval pathways depending on efficacy outcomes.