Telomir-Zn is an oral small molecule designed to target iron-dependent epigenetic mechanisms implicated in tumor-suppressor silencing.
TNBC still lacks a broadly actionable molecular target
Recent advances have expanded treatment options, but eligibility often depends on biomarker status or immunotherapy candidacy.
Telomir-Zn takes a different approach.
An oral small molecule targeting iron-dependent epigenetic machinery implicated in tumor-suppressor silencing.
Tumor-suppressor genes can be switched off through aberrant epigenetic activity. Iron-dependent KDM enzymes are implicated in this silencing, creating a targetable vulnerability.
Click to enlarge
Telomir-Zn enters the cell carrying zinc and exchanges it for excess intracellular iron. By reducing the iron available to fuel KDM enzyme activity, Telomir-Zn drives epigenetic reprogramming and reduces tumor DNA methylation. It also kills cancer cells in an iron-dependent manner.
Telomir -Zn
Iron(Fe)
Telomir -Fe
Zinc(Zn)
Telomir-Zn chelates excess intracellular iron (Fe2+/Fe3+), releasing protective zinc ions
Telomir -Zn
Telomir -Fe
Drug enters as Telomir-Zn; exits as Telomir-Fe after iron capture
Key differentiators: inhibits KDM2A, KDM2B, the KDM5 family, KDM6A/UTX, and KDM6B/JMJD3. Oral, once-daily mechanism with no approved drugs using the same approach.
By disrupting this iron-dependent epigenetic machinery, Telomir-Zn inhibits multiple KDM enzymes and promotes epigenetic reprogramming associated with reduced tumor-suppressor gene methylation.
Pancreatic (PANC-1): Concentration-dependent reduction in cell viability (IC50 = 38.6 µM) in a model known for treatment resistance.
vs. DFO (gold-standard chelator): Greater intracellular iron reduction at 6 hours.
Significant tumor volume suppression as oral monotherapy in a PC3 xenograft model.
Dose-dependent reduction in cell viability (IC50 = 1.6 µM), consistent with activity in hematologic malignancy.
Telomir-Zn demonstrated antitumor activity across multiple TNBC models.
Telomir-Zn significantly reduced primary tumor size, with greater activity observed when combined with paclitaxel.
Telomir-Zn significantly reduced primary tumor size and, at 3 µM, significantly reduced metastatic dissemination.
In a PC-3 prostate cancer xenograft model, oral Telomir-Zn significantly reduced tumor growth compared with vehicle. Telomir-Zn also reduced promoter methylation across the majority of tumor-suppressor genes evaluated, providing in vivo evidence consistent with its proposed epigenetic mechanism.
Click to enlarge
DNA Methylation Levels in Tumor Tissue
Cardiovascular, respiratory, phototoxicity, and repeat-dose toxicology studies were completed as part of the nonclinical package supporting FDA clearance of the Telomir-Zn IND.
