RVU120 as a single agent showed clinical benefit in heavily pretreated patients with AML and HR-MDS in the Phase 1 RIVER-51 study (CLI120-001). The strongest evidence of benefit was observed in patients with NPM1 and/or DNMT3A mutations and in patients with HR-MDS. A complete remission (CR) was achieved in a patient with NPM1 and DNMT3A mutations as well as 3 marrow CRs in patients with HR-MDS.
Preclinical results strongly support RVU120 as a candidate for venetoclax relapsed/refractory and frontline AML therapy.
New data in myelofibrosis models show that RVU120 acts synergistically with JAK inhibitors and BET inhibitor – pelabresib. These data support new potential therapeutic options for patients with myelofibrosis. Based on compelling preclinical results, Ryvu plans to launch the clinical study POTAMI-61 (NCT06397313).
KRAKOW, Poland, June 14, 2024 /PRNewswire/ -- Ryvu Therapeutics (WSE: RVU), a clinical-stage drug discovery and development company focusing on novel small molecule therapies that address emerging targets in oncology, presents clinical and preclinical data from RVU120 at the 2024 European Hematology Association Congress (EHA), June 13-16, Madrid, Spain.
"We are thrilled to share the advancements in RVU120 research and its clinical development, emphasizing its significant potential in addressing unmet needs in hematologic malignancies.", states Dr. Hendrik Nogai, Chief Medical Officer, Ryvu Therapeutics. "We are proud of the successful initiation of our Phase II studies. It is reassuring that the initial clinical safety data of RVU120 in combination with venetoclax, allow us to continue testing the compelling preclinical evidence of synergism in patients. Beyond AML and HR-MDS, we continue to work hard on new therapeutic strategies for patients with myeloproliferative neoplasms. Over the upcoming months, we are expecting a ramp up of patient enrollment and data readouts, and we remain committed to developing innovative treatments that can provide improved outcomes for patients in need." – underlines Dr. Hendrik Nogai, Chief Medical Officer, Ryvu Therapeutics.
Poster highlights:
Poster Title: RVU120, a first-in-class CDK8 inhibitor for the treatment of relapsed/refractory AML and high-risk MDS: preliminary results from two ongoing studies. Poster Number: P600
Session date and time: Friday, June 14 (9:00 CET on the online platform, 18:00 CET for the poster presentation)
The poster includes data on 30 evaluable patients out of 38 total dosed patients in the Phase I trial (RIVER-51) and initial data from the Phase II trial (RIVER-52).
RVU120 as single agent showed clinical benefit in heavily pretreated patients with AML and HR-MDS in the Phase I trial CLI120-001 (RIVER-51). The strongest evidence of benefit was observed in patients with NPM1 and/or DNMT3A mutations, and in patients with HR-MDS.
At the poster presentation's cut-off date, the data from the Phase II RIVER-52 trial of RVU120 as a monotherapy for patients with relapsed/refractory AML and HR-MDS were not yet mature enough for efficacy assessment in the target population, but preliminary signs of clinical benefit have been observed in ongoing patients.
The safety and tolerability of RVU120 at the RP2D of 250 mg administered every other day was confirmed in patients treated in both trials, with mild or moderate gastrointestinal events being the most frequently reported.
Poster Title: Synergistic potential of RVU120, a first-in-class CDK8/CDK19 inhibitor, with venetoclax in AML: preclinical and initial clinical insights. Poster Number: P525
Session date and time: Friday, June 14 (9:00 CET on the online platform, 18:00 CET for the poster presentation)
Ryvu presents a mechanism of synergy between RVU120 and venetoclax in preclinical models of acute myeloid leukemia (AML).
The combination of RVU120 and venetoclax leads to caspase-dependent degradation of MCL-1 protein and represses inflammatory and AML oncogenic pathways at the transcriptomic level in AML cells.
RVU120, when combined with venetoclax, exerts cytotoxic and differentiating effects on leukemic stem cells (LSCs) from a hierarchical AML model, exceeding the efficacy of venetoclax alone.
By countering therapeutic failure caused by persistent LSCs and MCL-1-mediated venetoclax resistance, this combination offers hope to patients with AML in both the refractory and the frontline setting.
Initial data from the ongoing Phase II study RIVER-81 demonstrate the safety of RVU120 in combination with venetoclax at the initial dose level in patients with relapsed/refractory AML. Enrollment is currently ongoing in Cohort 2.
Poster Title: CDK8/19 Inhibition: A Promising Therapeutic Strategy in Myeloproliferative Neoplasms. Poster Number: P1018
Session date and time: Friday, June 14 (9:00 CET on the online platform, 18:00 CET for the poster presentation)
In murine models of disease, RVU120 effectively attenuates myeloproliferative neoplasms (MPN) phenotypes (single-agent or combined with ruxolitinib (RUX)) partly through downregulation of pro-inflammatory cytokines.
RVU120 exhibits synergy with JAK inhibitors as a class and BET inhibitor – pelabresib. These findings open new potential therapeutic options for MPN patients, including myelofibrosis.
The combination of RVU120 and RUX acts synergistically by downregulating JAK/STAT signaling and inflammatory pathways at the transcriptomic level.
Based on compelling preclinical results, Ryvu is launching the clinical study POTAMI-61 (NCT06397313), evaluating RVU120 as a single agent or in combination with ruxolitinib in patients with myelofibrosis.
Ryvu Therapeutics is a clinical-stage drug discovery and development company focused on novel small-molecule therapies that address emerging targets in oncology. Internally discovered pipeline candidates use diverse therapeutic mechanisms driven by emerging knowledge of cancer biology, including small molecules directed at kinase, synthetic lethality, and immuno-oncology targets.
Ryvu's most advanced programs include RVU120, a selective CDK8/CDK19 kinase inhibitor with the potential to treat hematological malignancies and solid tumors, currently in Phase II development (i) as a monotherapy for the treatment of patients with relapsed/refractory acute myeloid leukemia (r/r AML) and high-risk myelodysplastic syndromes (HR-MDS) as well as (ii) in combination with venetoclax for the treatment of patients with r/r AML. Another clinical program, SEL24 (MEN1703), is a dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group. Ryvu Therapeutics has signed multiple partnering and licensing deals with global companies, including BioNTech and Exelixis.
The Company was founded in 2007 and is headquartered in Kraków, Poland. Ryvu is listed on the Warsaw Stock Exchange and is a component of the mWIG40 index. For more information, please see www.ryvu.com.
