Ryvu Therapeutics showcases RVU120 data at 2024 European Hematology Association Congress

Ryvu Therapeutics has presented promising clinical and preclinical data on RVU120, a novel therapeutic agent, at the 2024 European Hematology Association Congress held in Madrid, Spain. This clinical-stage company, headquartered in Krakow, Poland, specializes in developing small molecule therapies for oncology.

RVU120, a first-in-class CDK8 inhibitor, has shown significant clinical benefits in treating patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (HR-MDS). The Phase 1 study, RIVER-51 (CLI120-001), demonstrated that RVU120 provided clinical benefits in heavily pretreated patients. The most substantial evidence of its efficacy was observed in patients with NPM1 and DNMT3A mutations, as well as in those with HR-MDS. Notably, a complete remission was achieved in a patient with both NPM1 and DNMT3A mutations, and three marrow remissions were observed in HR-MDS patients.

In addition to its performance as a single agent, RVU120 has shown a synergistic effect when combined with other treatments. Preclinical studies indicate that RVU120 works synergistically with venetoclax, a therapy used for AML. The combination has shown promise in overcoming venetoclax resistance mediated by MCL-1 protein and persistent leukemic stem cells (LSCs). Initial data from the ongoing Phase II study, RIVER-81, support the safety of this combination, with patient enrollment continuing in Cohort 2.

Further, RVU120 has demonstrated potential in treating myelofibrosis (MF) when used in combination with JAK inhibitors and BET inhibitors such as pelabresib. Preclinical models suggest that RVU120 can effectively attenuate myeloproliferative neoplasm (MPN) phenotypes by downregulating pro-inflammatory cytokines and JAK/STAT signaling pathways. This has led to the launch of the POTAMI-61 clinical study (NCT06397313), which will evaluate RVU120 alone or in combination with ruxolitinib in patients with myelofibrosis.

During the congress, Ryvu Therapeutics presented multiple posters highlighting these findings. One poster detailed the preliminary results from ongoing studies of RVU120 in relapsed/refractory AML and high-risk MDS (Poster P600). Data from 30 evaluable patients in the Phase I trial and initial findings from the Phase II trial were showcased, confirming the safety and mild to moderate gastrointestinal tolerability of RVU120 at the recommended dose of 250 mg administered every other day.

Another poster (Poster P525) emphasized the synergistic potential of RVU120 with venetoclax in AML, showing how this combination leads to the degradation of the MCL-1 protein and repression of inflammatory and oncogenic pathways in AML cells. This combination has shown greater efficacy than venetoclax alone in preclinical models.

A third poster (Poster P1018) discussed the therapeutic strategy of CDK8/19 inhibition in myeloproliferative neoplasms. The data demonstrated RVU120's synergy with JAK inhibitors and BET inhibitors in preclinical models, opening new therapeutic possibilities for MPN patients.

Ryvu Therapeutics is optimistic about the future of RVU120 in treating hematologic malignancies and solid tumors. The company plans to continue its efforts in developing innovative treatments aimed at improving patient outcomes. With ongoing patient enrollment and data readouts expected in the coming months, Ryvu remains committed to addressing unmet medical needs in the field of oncology.