espi RYVU THERAPEUTICS S.A. 2023-12-11 18:30

Presentation of preclinical data on RVU120 at the 2023 American Society of Hematology (ASH) Annual Meeting and additional clinical update

The Management Board of Ryvu Therapeutics S.A. with its registered office in Krakow, Poland ("Company", "Ryvu") announces that additional preclinical data on RVU120, a selective CDK8/19 inhibitor, are presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, which is being held on December 9–12, 2023, in San Diego, California. These data supplement clinical and preclinical data on RVU120 reported in current report no. 48/2023 earlier today. Additionally, basing on the updated clinical data received on December 11, 2023, the Management Board reveals that an additional patient at the 250mg dose has achieved a morphologically leukemia-free state.

Details on the poster presentations are as follows: 

Abstract Title: “Targeting CDK8/CDK19 to Disrupt Leukemic Stem Cell-like Population in Acute Myeloid Leukemia: Exploring RVU120 As a Promising Frontline Therapy” 

Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III  

Session date and time: Monday, December 11, 2023, 2023, 6:00 PM - 8:00 PM PST 

Poster Number: 4175 

Leukemic stem cells (LSC) are a small subset of therapy-resistant AML cells and their eradication is essential for achieving cure in patients. In preclinical models, RVU120 displayed cytotoxic and differentiating effects on well-characterized leukemic stem cell (LSC) populations. The CDK8 activity marker is associated with LSC-rich bone marrow cells in AML patients, suggesting RVU120’s potential as an effective treatment for AML LSCs. In summary, RVU120 emerges as a frontline therapy candidate in AML treatment, addressing therapeutic failures caused by persistent LSCs in patients.

Abstract Title: “Mediator Kinase/CDK8 Inhibition as a Strategy to Improve FLT3 Inhibitor Activity in Acute
Myeloid Leukemia” 

Session Name: 604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III 

Session date and time: Monday, December 11, 2023, 6:00 PM-8:00 PM PST 

Poster Number: 4173 

The results demonstrate that inhibiting CDK8 with RVU120 (SEL120) can overcome mechanism of resistance to next generation of tyrosine-kinase inhibitors, such as gilteritinib. RVU120 in combination with gilteritinib resensitizes multiple FLT3-mutant AML cell lines, including these driven by RAS/MAPK activation. Activation of RAS/MAPK pathway occurs frequently in AML patients failing FTL3 inhibitors treatment. In vivo experiments demonstrate that the RVU120/gilteritinib combination extends survival in therapy-resistant AML models, providing further validation for the potential of FLT3/CDK8 inhibitors as a promising investigational strategy to pre-empt or overcome MAPK-mediated FLT3 TKI resistance. 

In addition, the Management Board informs that according to the new data received on December 11, 2023, an additional patient (111-001) treated at the 250mg dose, obtained a morphologically leukemia-free state (MLFS – bone marrow blasts < 5%; absence of circulating blasts; absence of extramedullary disease; no hematologic recovery required) with the reduction of blast count from 24% at the screening to 3% on C4D1 (day one of cycle four), and no detectable peripheral blasts. The patient is continuing study treatment and will be further monitored to assess the treatment outcome.

Disclaimer: This English language translation has been prepared solely for the convenience of English-speaking readers. Despite all the efforts devoted to this translation, certain discrepancies, omissions or approximations may exist. In case of any differences between the Polish and the English versions, the Polish version shall prevail. Ryvu Therapeutics S.A., its representatives and employees decline all responsibility in this regard.