Clinical trial published in Nature Medicine shows proof of concept of PAGE's therapeutic approach

BASEL, Switzerland, Jan. 24, 2025 /PRNewswire/ -- PAGE Therapeutics, a biotech company focused on tackling metastatic cancer spread at its root, is pleased to announce the publication of the results of a clinical study conducted by Prof. Nicola Aceto's team at ETH Zurich in collaboration with University Hospitals in Zurich, Liestal and Basel, Switzerland. The study design comprised measuring the effect of the cardiotonic agent digoxin (a widely used Na+/K+ ATPase inhibitor) in reducing the size of circulating tumor cells clusters, i.e. aggregates of tumor cells that travel in the bloodstream.

The presence of CTC clusters in patients' blood is associated with poor prognosis, and preclinical studies conducted by Prof Aceto and other groups have shown how CTCs have much higher potential to seed metastases when travelling as clusters rather than when traveling as single cells. Furthermore, in preclinical cancer models, treatment with Na+/K+ ATPase inhibitors enables the reduction of CTC clusters and metastases, opening up a new potential cancer treatment paradigm based on which PAGE Therapeutics was founded.

The present clinical study, published in the top-tier scientific journal Nature Medicine (link), has shown for the first time that the same effect on clusters can be achieved in humans. A cohort of 9 metastatic breast cancer patients were treated with digoxin for one week and evaluated against a control group. The primary endpoint – a reduction in size of CTC clusters – was met, with a statistically significant average reduction of 2.2 cells per cluster.

The study has previously been listed by Nature Medicine as one of the 11 clinical trials that could shape medicine in 2023.

PAGE Therapeutics owns an exclusive license on the use of digoxin and other existing Na+/K+ ATPase inhibitors in the prevention or treatment of metastasis, and, moreover, is developing new proprietary compounds purposely designed to maximize the dissolution of CTC clusters, which are showing much higher activity compared to digoxin in preclinical models.

"This trial is a remarkable proof-of-mechanism for the use of Na+/K+ ATPase inhibitors to disrupt CTC clusters in breast cancer," said Prof. Aceto, principal investigator of the study and co-founder of PAGE Therapeutics. "We administered a low digoxin dose for just one week, and yet we have seen a statistically significant result. With PAGE Therapeutics' new compounds, we are already able to dissolve clusters and block the formation of metastases in preclinical models far more efficiently than with digoxin, and with these results we are confident that we can translate these effects in humans. We are extremely excited to bring forward the development of this potentially game changing approach."

About Page

PAGE Therapeutics AG ('Page') is a Swiss preclinical-stage biotech company spun out of the ETHZ and founded on the groundbreaking science of Prof. Nicola Aceto. Page targets the vulnerabilities of tumor cells circulating in the bloodstream and is developing novel therapies that can disrupt their clusters, inhibiting their ability to form metastases.

Contact: media@pagetherapeutics.com

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