Flamingo Therapeutics Begins First Patient Dose in Danvatirsen AML/MDS Phase 1 Trial

Flamingo Therapeutics has recently announced the commencement of an Investigator-initiated Trial (IIT) to evaluate danvatirsen's safety and efficacy in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). These conditions, primarily affecting older adults, are challenging to treat and often result in relapse. Despite advancements in therapy, the prognosis for patients who relapse remains grim. Danvatirsen, discovered by Ionis, is a STAT3 inhibiting oligonucleotide currently being assessed as both a standalone treatment and in combination with venetoclax, a frontline therapy for relapsed or refractory AML and MDS.

The trial is being conducted at Montifore Einstein Comprehensive Cancer Center (MECCC) in New York and MD Anderson Cancer Center (MDACC) in Houston. Principal investigators for the trial include Dr. Aditi Shastri from MECCC and Dr. Naval Daver from MDACC. The study aims to address the critical need for more effective treatments for AML and MDS patients who have not responded to initial therapies.

Dr. Aditi Shastri expressed enthusiasm about the trial, emphasizing its potential to offer a novel therapeutic strategy for AML and MDS patients. She highlighted the collaborative nature of the study, which bridges academic research and industry efforts. The trial is supported by a multi-year grant from the US FDA Office of Orphan Products Development (OOPD), one of only ten such grants awarded in 2023.

Dr. Andrew Denker, Flamingo’s Chief Medical Officer, spoke positively about the collaboration with MECCC and MDACC and the momentum behind danvatirsen. He noted the significance of this trial in expanding Flamingo's clinical development program for danvatirsen, which is also being tested in head and neck cancers under the PEMDA-HN trial.

The Phase I IIT (NCT05986240) involves a sequential dose escalation design to evaluate danvatirsen as a monotherapy and in combination with venetoclax. The trial seeks to determine the safety, efficacy, pharmacokinetics, and pharmacodynamics of the drug, aiming to establish a recommended dose for Phase II studies and further investigations.

Flamingo Therapeutics is a leader in developing RNA-targeted therapies for cancer, focusing on undruggable transcription factors and long non-coding RNAs. The company has a strategic alliance with Ionis Pharmaceuticals and backing from prominent biotechnology investors. Flamingo is actively pursuing clinical trials for danvatirsen, including a Phase II trial (PEMDA-HN) for head and neck squamous cell carcinoma, alongside the newly initiated Phase I IIT for AML and MDS.

In conclusion, the initiation of the IIT marks a significant milestone in the clinical development of danvatirsen for treating challenging blood cancers. The collaboration between leading cancer research centers and Flamingo Therapeutics underscores the potential for innovative treatments to improve outcomes for patients with relapsed or refractory AML and MDS.