Telomir-Zn Suppresses Tumor Growth in TNBC and Prostate Cancer Models via Iron-Dependent KDM Inhibition, Preclinical Study Shows

Telomir PharmaceuticalsView company profile, Inc. (NASDAQ:TELO) announced the peer-reviewed publication of preclinical data demonstrating that its lead candidate, Telomir-Zn (search)Search drug, suppresses tumor growth in prostate and triple-negative breast cancer (search)Search disease (TNBC) models through selective modulation of intracellular iron and copper. The manuscript, titled "Telomir-Zn Modulates Intracellular Iron and Copper to Inhibit JmjC Histone Demethylases and Suppress Tumor Growth in Prostate and Triple-Negative Breast Cancer," was published in the Journal of Oncology Research and Therapy, Volume 11, Issue 3. These findings provide the scientific foundation for advancing Telomir-Zn toward a planned Phase 1/2 clinical trial in TNBC, for which the company has already received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration.

A Novel Iron-Dependent Mechanism of Action

The study's most critical finding was direct proof that Telomir-Zn (search)Search drug's anti-cancer activity depends on iron depletion. Histone demethylases, specifically the KDM2, KDM5, and KDM6 families, are often overexpressed in aggressive cancers, where they promote tumorigenesis by silencing tumor-suppressor genes or activating oncogenic programs. Telomir-Zn targets these KDM (search)Search target enzymes by depleting the intracellular iron they require for catalytic activity.

When researchers added iron back to treated TNBC cells, the compound's killing effect was significantly reversed. This iron-rescue result, according to the publication, eliminates alternative explanations and demonstrates that the mechanism is real and specific, rather than a general toxin or off-target effect.

"Overactive KDM (search)Search target enzymes also play a role as important drivers of this epigenetic silencing. Current TNBC treatments address downstream consequences of this dysregulation but do not target the KDM-driven mechanism itself," said Dr. Itzchak Angel, Chief Scientific Advisor of Telomir. "Our data implicates that by reversing the abnormal methylation and by KDM inhibition, Telomir-Zn (search)Search drug can reactivate these silenced tumor-suppressor genes, promoting cell killing."

Selective Targeting and Tumor Suppressor Reactivation

Telomir-Zn (search)Search drug demonstrated a notable selectivity profile, killing iron-dependent TNBC cancer cells at low concentrations while leaving normal cells unharmed at concentrations more than 50-fold higher. This selectivity window indicates the compound preferentially targets cancer cells with elevated iron dependence, a hallmark of aggressive malignancies like TNBC.

In a prostate cancer (search)Search disease model, oral Telomir-Zn (search)Search drug suppressed tumor growth and reactivated silenced tumor-suppressor genes, including STAT1, GSTP1, RASSF1A, CDKN2A, and MASPIN. The compound works through an upstream mechanism distinct from approved drugs that target downstream epigenetic machinery, such as DNMT or HDAC inhibitors. By depleting labile iron and disabling KDM (search)Search target enzymes, Telomir-Zn disrupts epigenetic silencing at its root.

Anti-Tumor and Anti-Metastatic Activity in Xenograft Models

In TNBC human xenograft models, Telomir-Zn (search)Search drug reduced primary tumor size across several cell lines. In HCC1806 xenografts, the compound also significantly reduced metastatic dissemination—a finding of particular clinical relevance, as most TNBC patients die from spread disease rather than the primary tumor.

In BT-549 xenografts, Telomir-Zn (search)Search drug combined with paclitaxelView drug details produced significantly greater tumor reduction than either drug alone, suggesting potential for combination therapy approaches in the clinic. Notably, MDA-MB-231 xenografts did not respond, indicating heterogeneous sensitivity based on tumor-specific iron-metabolism features. This differential response suggests the possibility of future patient stratification based on personalized iron-handling signatures to enrich for responders in clinical development.

Addressing an Unmet Need in TNBC

Triple-negative breast cancer (search)Search disease remains a significant clinical challenge. Most patients receive chemotherapy as a backbone, with limited options for targeted or precision-based approaches. Current approved therapies address symptoms of epigenetic dysregulation but do not target the underlying metabolic drivers—specifically, the dysregulated iron homeostasis that fuels overactive KDM (search)Search target enzymes in iron-addicted cancers.

"Triple-negative breast cancer (search)Search disease represents one of oncology's most significant unmet needs," said Erez Aminov, CEO of Telomir. "Most patients with advanced disease have limited treatment options and poor survival outcomes. We're excited to advance Telomir-Zn (search)Search drug into our Phase 1/2 program under our active IND to test whether this approach can meaningfully improve outcomes for TNBC patients."

The publication establishes dysregulated KDM (search)Search target-driven epigenetic silencing as a fundamental cancer vulnerability that can be targeted through selective iron modulation. The preclinical anti-metastatic activity observed in HCC1806 xenografts is particularly noteworthy, as it suggests the potential to address both primary tumor control and disseminated disease—a key unmet need in TNBC. The iron-rescue experiments provide the strongest possible proof of mechanism, enabling clinical strategies for patient selection based on iron-metabolism biomarkers as the program advances into human trials.