ATX-101

First-in-class modulator of PCNA-mediated stress responses

ATX-101 is a first-in-class peptide therapeutic that targets stress-induced protein interactions with Proliferating Cell Nuclear Antigen (PCNA), a master regulator of cellular stress responses. By disrupting these interactions, ATX-101 sensitizes cancer cells to anticancer therapy while sparing the essential functions of PCNA in normal cell replication¹.

Why PCNA?

PCNA is best known for its essential role in DNA replication and repair, but extensive research has demonstrated that it also coordinates multiple stress-response pathways involved in:

DNA damage tolerance
Cell survival and apoptosis
PI3K/AKT/mTOR signalling
Cellular metabolism
Immune regulation

Cancer cells rely heavily on these adaptive stress responses to survive treatment.

How ATX-101 works

ATX-101 contains APIM, a peptide motif that selectively interferes with stress-induced PCNA protein interactions. Rather than inhibiting PCNA itself, ATX-101 disrupts the stress defense mechanisms that cancer cells activate during treatment with anti-cancer therapy. This unique mechanism enhances the activity of multiple anticancer treatments (e.g. cisplatin²or temozolomide/radiotherapy³) maintaining a favourable safety profile⁴.

Clinical potential

ATX-101 has demonstrated:

Broad antitumour activity across multiple cancer models
Synergy with chemotherapy and other anticancer agents
Clinical safety in Phase I studies
Encouraging signs of efficacy in combination therapy

ATX-101 is currently being advanced in combination strategies for difficult-to-treat solid tumours.

For more information on the mechanism of ATX-101, see Intervention Point or Publications.

Müller R et al, 2013. Targeting proliferating cell nuclear antigen and its protein interactions induces apoptosis in multiple myeloma cells. PLoS One. 2013 Jul 31;8(7); unpublished data.
Søgaard CK et al, 2018. “Two hits - one stone”; increased efficacy of cisplatin-based therapies by targeting PCNA’s role in both DNA repair and cellular signaling. Oncotarget, 2018, Vol. 9, (No. 65), pp: 32448-32465.
Gravina GL et al, 2022. ATX-101, a peptide targeting PCNA, has antitumor efficacy alone or in combination with radiotherapy in murine models of human glioblastoma. Cancers. 2022, 14, 289.
Lemech CR et al, 2022. ATX-101, a cell-penetrating protein targeting PCNA, can be safely administered as intravenous infusion in patients and shows clinical activity in a Phase 1 study. Oncogene, 2022 Dec 23.