REM-422, an oral small-molecule mRNA degrader targeting MYB, produced a 43% overall response rate by RECIST in the efficacy population of an ongoing Phase 1 trial in recurrent or metastatic adenoid cystic carcinoma. In biomarker-positive patients on study for more than six months, 71% showed tumor shrinkage greater than 20%, with six partial responses, four of which are confirmed and ongoing at four to six months. Pharmacokinetics were linear across dose levels, on-target activity was demonstrated via reductions in MYB mRNA and protein in tumor biopsies, and the agent was generally well tolerated; the most common treatment-related adverse events at the recommended Phase 2 dose were anemia, fatigue, and epistaxis.
The core development is preliminary proof-of-mechanism and early proof-of-concept in ACC for a first-in-class RNA processing modulator, with data presented at a major molecular therapeutics meeting. The open-label study includes dose escalation and expansion, the latter focused on biomarker-selected patients, and is intended to establish the RP2D and characterize antitumor activity. While denominators and full baseline characteristics for the efficacy analysis were not disclosed, the observed responses compare favorably to historical benchmarks in ACC, a setting without approved systemic therapies, and support continued expansion. REM-422 also holds U.S. Orphan Drug Designation in ACC and AML and is being evaluated separately in AML or high-risk MDS.
Strategically, this is both a validation of Remix’s RNA processing platform and a targeted bet on a transcription factor long viewed as intractable. The choice to concentrate early development in a MYB-driven rare tumor creates a plausible accelerated-approval path built around single-arm ORR and durability, while generating translational evidence that can de-risk broader programs. It also positions the company ahead of would-be competitors approaching MYB indirectly through epigenetic or cofactor pathways. The tension is clear: enthusiasm around a first human signal must be balanced against small-sample, early-cut data, partial confirmation status, and limited follow-up. Additionally, the safety profile will be scrutinized for class effects related to splicing modulation, particularly hematologic events as dosing intensifies or combinations are explored.
For sites and CROs, an oral agent with manageable toxicity and measurable on-target biomarkers can streamline enrollment and monitoring, but it adds operational complexity around tissue access for serial biopsies and standardized MYB assays. Central lab capacity and assay harmonization will matter if biomarker selection tightens. Sponsors running rare tumor portfolios will watch whether ACC can serve as a registrational foothold for RNA processing agents, potentially shifting resourcing toward single-arm designs with deep translational endpoints. Regulators are likely to focus on durability, consistency across sites and assay platforms, and the definition and prospective use of the biomarker-positive population.
Next steps will pivot on locking the RP2D, expanding the biomarker-selected cohort, and maturing response durability to the 6–12 month window that could underpin regulatory dialogue for an accelerated pathway. Clarity on the efficacy population size, confirmed response rate, disease control, and median duration of response will be decisive, as will evidence that off-target splicing does not erode tolerability with longer exposure. Beyond ACC, the company’s stated intent to move into MYB-driven leukemias and solid tumors raises new hurdles, including different regulatory standards in hematology and potential need for combinations. Watch for assay standardization, durability updates, and any signal of activity outside ACC as indicators of whether REM-422 is a niche rare-tumor play or the start of a broader RNA processing franchise.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
