News - ATX-101 - LARVOL VERI

1year

Multiple Myeloma Cells with Increased Proteasomal and ER Stress Are Hypersensitive to ATX-101, an Experimental Peptide Drug Targeting PCNA. (PubMed, Cancers (Basel))

Interestingly, carfilzomib-resistant cells were at least as sensitive to ATX-101 as the wild-type cells, suggesting both low cross-resistance between ATX-101 and proteasome inhibitors and elevated proteasomal stress in carfilzomib-resistant cells. Our multi-omics approach revealed a vital role of PCNA in regulation of proteasomal and ER stress in MM.

1 year ago

Journal • IO biomarker

PCNA (Proliferating cell nuclear antigen) • LILRB4 (Leukocyte Immunoglobulin Like Receptor B4) • FADS2 (Fatty Acid Desaturase 2) • TSG101 (Tumor Susceptibility 101)

carfilzomib • ATX-101

2years

A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy (clinicaltrials.gov)

P1/2, N=16, Terminated, THERAPIM PTY LTD | Phase classification: P1b/2a --> P1/2 | N=78 --> 16 | Trial completion date: Mar 2025 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Mar 2025 --> Nov 2023; For technical reasons, it was decided by the sponsor to close the ongoing ovarian cancer study, AM ATX101-03, immediately.

2 years ago

Phase classification • Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy

carboplatin • pegylated liposomal doxorubicin • ATX-101

almost3years

ATX-101, a peptide drug targeting PCNA, enhances the effect of gemcitabine in liposarcoma and leiomyosarcoma (AACR 2023)

Two of the most common sarcomas are liposarcoma and leiomyosarcoma which are often treated with chemotherapies such as doxorubicin, dacarbazine and gemcitabine with low response rates...Enhanced combination effects with ATX-101 and chemotherapies such as doxorubicin, irinotecan and gemcitabine were also observed by proliferation assay...Tumor target inhibition by western blot showed increased pH2A.X and cleaved PARP along with decreased RAD51 API protein with combination treatment. Taken these observations and results, there is strong evidence of combining gemcitabine with ATX-101 in liposarcoma and leiomyosarcoma.

almost 3 years ago

PARP Biomarker

RAD51 (RAD51 Homolog A) • CASP3 (Caspase 3) • CCNA2 (Cyclin A2) • PCNA (Proliferating cell nuclear antigen) • ALKBH2 (AlkB Homolog 2) • CCNB1 (Cyclin B1)

gemcitabine • doxorubicin hydrochloride • irinotecan • dacarbazine • ATX-101

3years

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. (PubMed, Oncogene)

Further studies have been initiated to provide evidence of efficacy. Trial registration numbers: ANZCTR 375262 and ANZCTR 375319.

3 years ago

P1 data • Journal

PCNA (Proliferating cell nuclear antigen)

ATX-101

almost4years

A phase II study, with a safety lead-in, to evaluate ATX-101, a peptide drug targeting PCNA, in advanced dedifferentiated liposarcoma and leiomyosarcoma. (ASCO 2022)

Tissue is used for correlative analysis interrogating ATX-101’s effects on the immune microenvironment through multiplex immunohistochemistry, DNA damage response through whole exome sequencing/RNAseq to evaluate for alterations in HR pathway component genes, and intracellular signaling pathways by Western blot for AKT/mTOR components. The study opened to accrual 12/2021.

almost 4 years ago

Clinical • P2 data

PCNA (Proliferating cell nuclear antigen) • ALKBH2 (AlkB Homolog 2)

ATX-101

4years

ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma. (PubMed, Cancers (Basel))

In line with the in vitro results, ATX-101 strongly reduced tumor growth in two subcutaneous xenografts and two orthotopic GBM models, both as a single agent and in combination with RT. The ability of ATX-101 to sensitize cells to RT is promising for further development of this compound for use in GBM.

4 years ago

Preclinical • Journal • Combination therapy

PTEN (Phosphatase and tensin homolog) • PCNA (Proliferating cell nuclear antigen)

ATX-101

almost5years

[VIRTUAL] Safety profile and disease stabilization in late stage, heavily pretreated, solid tumor patients in a first-in-human (FIH) study of ATX-101, a drug targeting proliferating cell nuclear antigen (PCNA). (ASCO 2021)

ATX-101 is well tolerated at all dose levels with IRRs being the most frequent AEs . Drug exposure is dose dependent with rapid plasma clearance, which confirms in vivo data demonstrating the quick uptake by cells of all organs . The observed duration of SD may be attributed to ATX-101 activity .

almost 5 years ago

Clinical • P1 data

PCNA (Proliferating cell nuclear antigen)

ATX-101