On January 13, 2022 APIM Therapeutics (APIM), a clinical stage biotech company, focusing on the development of novel peptide therapeutics targeting PCNA (Proliferating Cell Nuclear Antigen), reported the publication of research data of ATX-101 in glioblastoma preclinical models in the peer reviewed journal Cancers (Press release, APIM Therapeutics, JAN 13, 2022, View Source,c3485004 [SID1234605480]).

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The article entitled "ATX-101, a Peptide Targeting PCNA, has antitumor efficacy alone or in combination with Radiotherapy in murine models of human glioblastoma" investigated ATX-101, the lead compound of APIM’s development program, in a panel of human glioblastoma (GBM) and patient-derived glioma-initiating cells (GICs) in vitro and in vivo alone or in combination with Radiotherapy (RT). The study was a collaboration between APIM Therapeutics and the laboratory of Dr. Festuccia at the Department of Biotechnological and Applied Clinical Sciences, Laboratory of Radiobiology, University of L’Aquila, Italy.

In the study, it was shown that ATX-101 has anticancer activity as a single agent in vitro and in vivo. Furthermore, ATX-101 potentiated the effect of RT in both subcutaneous and intracranial xenograft tumor models. ATX-101 affected key oncogenic signaling pathways such as AKT/mTOR and DNA-PKcs; a correlation between high AKT activation and sensitivity to ATX-101 was also observed. Finally, ATX-101 increased the levels of γH2AX, DNA fragmentation, and apoptosis when combined with RT.

"The results obtained in glioblastoma models are in agreement with previous preclinical investigations of ATX-101 conducted in a large variety of tumor models" said Professor Marit Otterlei, CSO of APIM Therapeutics. "Our data suggest that targeting the stress regulatory mechanisms of PCNA holds therapeutic promise in glioblastoma tumors".

"The fact that ATX-101 exhibits therapeutic activity and potentiates the effect of RT in GBM opens up new clinical development opportunities for APIM Therapeutics" stated Dr. Kostas Alevizopoulos, CEO of APIM. "This could help provide a new therapeutic option for this deadly disease to be tested in human clinical trials."

The article co-authored by Dr M. Otterlei, Dr C. Festuccia and coworkers and published in Cancers (January 7, 2022) can be accessed here: View Source

About ATX-101

ATX-101 is a first-in-class, cell penetrating peptide featuring a novel PCNA-interacting motif (AlkB homolog 2 PCNA Interacting Motif or APIM). In preclinical experiments, it was shown that APIM-containing proteins bind to PCNA and mediate processes of escape mechanisms and survival of cancer cells. ATX-101 competitively inhibits interaction of PCNA with APIM-containing protein complexes resulting in cancer cell death and altered cellular signaling. These properties translate in anticancer effects of ATX-101 as demonstrated in several preclinical models in vitro and in vivo. Currently, ATX-101 is in clinical development for ovarian cancer (phase 1b/2a) and sarcoma (phase 2).