- Clinically meaningful benefit of RVU120 monotherapy: a complete remission (CR) in a DNMT3A/NPM1-mutated AML patient; more than 18-month duration of therapy in a DNMT3A-mutated high-risk MDS patient; stable diseases (SD) with blast reductions in three additional patients

- Partner Menarini Group presents updated data from Phase 1/2 study of SEL24 (MEN1703), in patients with IDH1/2-mutated AML

KRAKOW, Poland, June 10, 2022 /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, today announced updated data from the ongoing Phase 1b dose-escalation study of RVU120 in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (HR-MDS) at the Annual European Hematology Association (EHA) 2022 Hybrid Congress, June 9-17 in Vienna, Austria. In addition, Ryvu's partner, Menarini Group, presented a clinical update on the Phase 1/2 study of SEL24 (MEN1703) in patients with IDH1/2-mutated AML.

"The data presented at this year's EHA Congress demonstrate Ryvu's commitment to developing effective, first-in-class treatment options for people with hematologic malignancies," said Hendrik Nogai, M.D., Chief Medical Officer at Ryvu Therapeutics.

"We are excited to share these promising results from our ongoing Phase 1b dose-escalation study in patients with AML and HR-MDS, in which we have seen single-agent activity of RVU120, validating its mechanism of action even at doses that resulted in less than complete target engagement. These clinical data support our responder hypothesis in a molecularly defined subset of patients with DNMT3A and NPM1 mutations. Based on the encouraging data, we plan to continue dose escalation and further advance the clinical development of RVU120 in both biomarker-selected AML patients and the unselected broader AML population."

"The emerging RVU120 clinical data are very promising with the potential to achieve durable benefit in patients with very few treatment options," said Pawel Przewiezlikowski, CEO of Ryvu Therapeutics. "We are also proud that the SEL24 (MEN1703) program, developed in collaboration with our partner Menarini, continues to make progress in the clinic. We look forward to providing future updates from our clinical programs throughout 2022 as we advance new and innovative therapeutics for patients suffering from cancer."

Poster presentations featured at the Congress:

RVU120: orally available CDK8/19 inhibitor

Abstract Title: "CLI120-001 Phase1b Dose Escalation Study of RVU120 in Patients with AML or High-Risk MDS Safety and Efficacy Data Update," Abstract Number: #P501

Preliminary results were presented from the first seven cohorts, demonstrating a favorable safety and a predictable pharmacokinetic (PK) profile for RVU120.

As of the data cutoff date of May 26, 2022, 16 patients with AML or HR-MDS have been dosed (5 ongoing) with a median of three prior lines of therapy.

Clinically meaningful benefit of RVU120 monotherapy has been observed at doses that resulted in less than complete target engagement, with one complete remission (CR) and stable diseases with blast reductions in several ongoing patients who failed multiple prior lines of therapy and presented with a very poor prognosis:

  • Complete remission in an AML patient with FLT3/DNMT3A/NPM1 mutations
  • Stable disease with a duration of therapy of more than 18 months in a high-risk MDS patient with DNMT3A mutations; significant reductions in red blood cells (RBC) transfusions at various timepoints
  • Three additional patients ongoing with stable disease and blast count reductions

Dose escalation is ongoing, with active enrollment in the 100 mg dose cohort (NCT04021368).

Abstract Title: "Preclinical and Clinical Signs of RVU120 Efficacy, a Specific CDK8/19 Inhibitor in DNMT3A Mutation Positive AML and HR-MDS," Abstract Number: #P450 

Preclinical data demonstrate that treatment with RVU120 demonstrated a pronounced anti-cancer effect in AML patient-derived cells with DNMT3A and NPM1 mutations.

Preliminary evidence of clinical response to RVU120 has been shown in a r/r AML patient with DNMT3A and NPM1 mutations, who achieved a complete remission.  Anti-cancer efficacy of RVU120 was associated with transcriptomic reprogramming involving lineage commitment and inhibition of homeobox genes. Repression of homeobox genes in the responder patient confirms the on-target activity of RVU120.

Further molecular studies in a larger number of patients under RVU120 treatment are ongoing and are expected to provide additional evidence for predictive markers of response to RVU120 in AML.

SEL24/MEN1703: orally available dual PIM/FLT3 inhibitor

Abstract Title: "Phase 1/2 Study of SEL24/MEN1703, a First-In-Class Dual PIM/FLT3 Kinase Inhibitor, in Patients with IDH1/2-Mutated Acute Myeloid Leukemia: The DIAMOND-01 Trial," Abstract Number: #P520

Ryvu's partner Menarini Group reported the updated safety and efficacy results from an additional expansion cohort of the DIAMOND-01 trial, which enrolled patients with relapsed or refractory (R/R) IDHm AML, treated with the dual PIM/FLT3 inhibitor, SEL24 (MEN1703).

As of a data cutoff of April 21, 2022, 25 patients were enrolled in the IDHm AML expansion cohort. SEL24 (MEN1703) was well tolerated, with no drug discontinuations or deaths due to treatment-related adverse events (TRAEs). Promising efficacy was observed, with overall response rates (ORR) and complete remission (CR) / CR with incomplete hematologic recovery (CRi) / CR with partial hematologic recovery (CRh) of 13% for the IDHm cohort, which is similar to monotherapy activity of other drugs in R/R AML.

Based on these data, SEL24/MEN1703 may be a feasible therapy in this difficult-to-treat population of patients with R/R AML who harbor IDH mutations. Clinical trials are planned in order to better explore the potential of SEL24/MEN1703 in different AML populations.

All posters are now available for download from Ryvu corporate website: https://ryvu.com/investors-media/publications/.

About Ryvu Therapeutics  

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 make use of 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 are RVU120 - a selective CDK8/CDK19 kinase inhibitor with potential for the treatment of hematological malignancies and solid tumors currently in Phase I clinical development for the treatment of acute myeloid leukemia and myelodysplastic syndrome, and Phase I/II for the treatment of r/r metastatic or advanced solid tumors, and SEL24 (MEN1703) - dual PIM/FLT3 kinase inhibitor licensed to the Menarini Group, currently in Phase II clinical studies in acute myeloid leukemia.

The company was founded in 2007 and is headquartered in Krakow, Poland. Ryvu is listed on the main market of the Warsaw Stock Exchange and is a component of the sWIG80 index. For more information, please see www.ryvu.com.

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SOURCE Ryvu Therapeutics

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