FDA lifts Partial Clinical Hold on Phase Ib Clinical Trial of RVU120 (SEL120) in Acute Myeloid Leukemia and Myelodysplastic Syndrome

KRAKOW, Poland, July 14, 2021 /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, announced today that the U.S. Food and Drug Administration, FDA, has lifted a partial clinical hold, previously announced on April 8, 2021, on the first-in-human (FIH) Phase Ib, dose escalation clinical trial of RVU120 (also known as SEL120) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (high-risk MDS), being conducted in the United States. 

"We are thankful to FDA for working with us in a swift and interactive manner to review the data from the trial and introduce modifications to the study protocol. We believe that the initially demonstrated benefit of treatment with RVU120 as a single agent for AML and MDS patients, coupled with the amended study protocol will lead to a safe, timely and successful completion of the clinical trial. We will be working closely with the investigators and the clinical sites to obtain IRBs' approvals on the revised protocol and resume patient enrollment in Q3 2021" – said Pawel Przewiezlikowski, Chief Executive Officer of Ryvu.

Based on the recommendations from the FDA, the study will resume enrollment at a 75mg dose (Every Other Day – EOD) in a standard 3+3 design, according to a revised protocol intended to increase patients' safety. Protocol amendment covers modified exclusion criteria, scope of monitoring and frequency of laboratory testing. Following the completion of the 75mg cohort, the data generated will be reviewed by the agency and a further dose escalation strategy will be established. Additionally, Ryvu plans to use 75mg as the starting dose for the single-agent, open-label Phase I/II trial investigating the safety and efficacy of RVU120 in patients with relapsed/refractory metastatic or advanced solid tumors, which will commence patient enrollment in Q3.

The partial clinical hold was issued following Ryvu's recent report to the FDA of a Serious Adverse Event (SAE) involving a patient death that may possibly be related to RVU120. Study enrollment was suspended but patients already on treatment could continue treatment.  As of July 14, 2021 one patient still remains on RVU120 treatment.

The initial safety and efficacy data from the first four cohorts in the trial were presented at the Virtual EHA Congress on June 11, 2021. RVU120 demonstrated acceptable safety profile and two clinically relevant responses were observed in the first five AML and high-risk MDS patients treated: one complete response (CR) and one erythroid response.

About RVU120

RVU120 (SEL120) is a selective first-in-class CDK8/CDK19 inhibitor, which has demonstrated efficacy in a number of solid tumor types in in vitro and in vivo models as well as in onco-hematological malignancies. The first-in-human phase I study with RVU120, in relapsed or refractory AML or high-risk MDS, will resume enrollment of patients at 5 investigational sites in USA (https://clinicaltrials.gov/ct2/show/NCT04021368). Additional sites are planned to be activated in Poland in Q3 2021.

The initial safety and efficacy data from the first four cohorts in the trial was presented at the Virtual EHA Congress on June 11, 202. RVU120 demonstrated acceptable safety profile and two clinically relevant responses were observed in the first five AML and high-risk MDS patients treated: one complete response (CR) and one erythroid response.

Translational data suggest that RVU120 is particularly effective in undifferentiated AML STAT5-positive cancers. Administration of RVU120 in orthotopic AML patient derived xenograft models reduced tumor burden to the level undetectable in the peripheral blood, decreased splenomegaly and resulted in partial bone marrow recovery at well tolerated doses.

In addition, RVU120 has demonstrated single agent efficacy in multiple solid tumor models. On May 28, 2021, Ryvu's Clinical Trial Application (CTA) to commence a single-agent, open-label Phase I/II trial, investigating the safety and efficacy of RVU120 in patients with relapsed/refractory metastatic or advanced solid tumors, was approved by the Polish Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, and the respective Central Ethics Committee.

On March 25, 2020, the U.S. Food and Drug Administration (FDA) granted an orphan drug designation (ODD) to RVU120, for the treatment of patients with AML.

RVU120 (SEL120) has been internally discovered by Ryvu and has received support from the Leukemia & Lymphoma Society Therapy Acceleration Program® (TAP), a strategic initiative to partner directly with innovative biotechnology companies and leading research institutions to accelerate the development of promising new therapies for blood cancers.

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. RVU120 is a selective CDK8/CDK19 kinase inhibitor with potential for the treatment of hematological malignancies and solid tumors currently in Phase 1b clinical development for the treatment of acute myeloid leukemia and myelodysplastic syndrome. SEL24 (MEN1703) is a 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 (until 2019 operating under the name Selvita S.A.) and currently employs over 160 associates, including more than 80 PhDs. Ryvu is headquartered in Krakow, Poland, listed on the main market of the Warsaw Stock Exchange, and is a component of sWIG80 index. For more information, please see www.ryvu.com.

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SOURCE Ryvu Therapeutics