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imetelstat + venetoclax
- Development stage
- Unknown
- Lead developer
- AbbVie
- Modality
- Small Interfering RNA (siRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, MicroRNA (miRNA) → Small RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Single-strand DNA → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Modified DNA Oligonucleotides → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Rytelo + venetoclax is an investigational drug combination consisting of Rytelo (imetelstat), a first-in-class telomerase inhibitor, and venetoclax, a selective B-cell lymphoma 2 (BCL-2) inhibitor. Imetelstat is a lipid-conjugated 13-mer oligonucleotide that binds to the RNA template region of telomerase (TERC), inhibiting its activity and leading to telomere shortening and apoptosis in cancer cells. Venetoclax is an oral small-molecule BH3-mimetic that selectively binds to and inhibits the anti-apoptotic protein BCL-2, restoring the apoptotic pathway in cancer cells. Preclinical studies have demonstrated synergistic anti-leukemic activity of the combination in acute myeloid leukemia (AML) cell lines and patient-derived samples, showing enhanced apoptosis and prolonged survival in xenograft models. The combination is being clinically evaluated in the Phase 1 IMAGINE trial (NCT07320235) in combination with azacitidine for the treatment of patients with relapsed or refractory AML.
- Other names
- GRN163L + ABT-199GRN163L + GDC-0199Rytelo + VenclextaRytelo + VenclyxtoRytelo + venetoclaximetelstat + ABT-199imetelstat + GDC-0199imetelstat + Venclextaimetelstat + Venclyxto
02
Targets
BCL-2 (BCL-2 family)TERC (Telomerase RNA component)
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