ATX-101 / APIM Therap - LARVOL DELTA

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."

IO biomarker • Journal • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • FADS2 • LILRB4 • PCNA • TPD52 • TSG101

A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy (clinicaltrials.gov) - P1/2 | N=16 | Terminated | Sponsor: 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.

Combination therapy • Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Trial termination • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

ATX-101 in Advanced Dedifferentiated Liposarcoma and Leiomyosarcoma (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: Columbia University | N=34 ➔ 4 | Trial completion date: Feb 2026 ➔ Oct 2022 | Recruiting ➔ Terminated | Trial primary completion date: Feb 2023 ➔ Oct 2022; Study terminated by PI

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Solid Tumor

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."

Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ALKBH2 • CASP3 • CCNA2 • CCNB1 • PCNA • RAD51

PCNA regulates primary metabolism by scaffolding metabolic enzymes. (PubMed, Oncogene) - "In addition, we show that ATX-101 treatments reduced the ENO1 - PCNA interaction, the ENO1, GAPDH and 6PGD protein levels, as well as the 6PGD activity. Here we report for the first time that PCNA acts as a scaffold for metabolic enzymes, and thereby act as a direct regulator of primary metabolism."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • ENO1 • GAPDH • PCNA

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."

Journal • P1 data • Oncology • Solid Tumor • PCNA

Nordic Nanovector and APIM Therapeutics Announce Merger Agreement (Market Screener) - "ATX-101 is currently being evaluated in platinum-sensitive ovarian cancer (Phase 1b/2a) and sarcoma (Phase 2) patients. Two pilot clinical studies, evaluating ATX-101 in platinum-resistant ovarian cancer and glioblastoma are expected to start in the second half of 2023."

New trial • Trial status • Brain Cancer • CNS Tumor • Glioblastoma • Gynecologic Cancers • Oncology • Ovarian Cancer • Sarcoma

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) - P2 | "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."

Clinical • P2 data • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ALKBH2 • PCNA

A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy (clinicaltrials.gov) - P1b/2a | N=78 | Recruiting | Sponsor: THERAPIM PTY LTD | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

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."

Combination therapy • Journal • Preclinical • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • PCNA • PTEN

A Study to Evaluate the Combination of ATX-101 and Platinum-based Chemotherapy (clinicaltrials.gov) - P1b/2a; N=78; Not yet recruiting; Sponsor: THERAPIM PTY LTD; Initiation date: Apr 2021 ➔ Sep 2021

Combination therapy • Trial initiation date • Endometrial Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • MRI

[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 ."

Clinical • P1 data • Oncology • Solid Tumor • PCNA • Tryptase

Histological Analysis of the Effect of ATX-101 (Deoxycholic Acid Injection) on Subcutaneous Fat: Results From a Phase 1 Open-Label Study. (PubMed, Dermatol Surg) - "Subcutaneous injection of ATX-101 induces adipocytolysis and local inflammation with septal thickening and resolution of inflammation by 28 days after injection."

Clinical • Journal • P1 data