Rakovina Therapeutics Announces Publication Highlighting Activity of Novel Bifunctional PARP-HDAC Inhibitors in Preclinical Models of Ewing’s Sarcoma, The Canadian Business Journal

The publication will be made available on the preprint server, Bio Rxivis submitted for peer review in scientific journals

VANCOUVER, British Columbia, November 14, 2022 (GLOBE NEWSWIRE) — Rakovina Therapeutics Inc. (TSX-V: RKV) (the “Company”) today announced the publication of a scientific article on the anti-cancer effects of its novel Announced. Dual PARP-HDAC inhibitors in a model of Ewing’s sarcoma.

Manuscript Entitled “Bifunctional PARP-HDAC Inhibitor with Activity in Ewing’s Sarcoma” Demonstrates Benefits of Dual PARP and HDAC Inhibition and Provides Proof-of-Concept for Bifunctional Single Molecule Therapeutic Strategy in Ewing’s Treatment sarcoma.

Ewing sarcoma is a highly aggressive bone and soft tissue tumor that primarily affects children and young adults, with dismal 5-year survival rates of 15-30% for metastatic disease. Previous studies have shown that Ewing sarcoma cells are sensitive to FDA-approved PARP inhibitors, but clinical trials have failed to produce durable therapeutic responses.

PARP inhibitors have been demonstrated to affect tumors harboring BRCA mutations or other defects in homologous repair (HR). This concept is commonly referred to as “BRCAness”.

Ewing sarcoma is characterized by the presence of gene fusions involving the EWSR1 gene. This fusion has been shown to impair HR activity indicative of levels of ‘BRCAness’ in Ewing sarcoma. The lack of clinical response in Ewing sarcoma to treatment with single-agent PARP inhibitors supports the adoption of combination therapy strategies that further inhibit HR and increase BRCAness in Ewing sarcoma.

Recent studies in leukemia, breast cancer, liver cancer, glioblastoma, prostate cancer, and anaplastic thyroid models have demonstrated suppression of HR after treatment with HDAC inhibitors, demonstrating dual inhibition of HDAC and PARP. The possibility of synergistic effects is supported.

Rakovina Therapeutics researchers have characterized and tested kt-3283, a novel dual-function single molecule of PARP and HDAC in an Ewing sarcoma model system. In these studies, kt-3283 was more efficacious than treatment with single-agent PARP or HDAC inhibitors. These data show that the dual activity of kt-3283 is 30- to 80-fold more potent in the Ewing sarcoma model than the FDA-approved PARP inhibitors and 30- to 60-fold more potent than the FDA-approved HDAC inhibitors. indicates that there is In an Ewing’s sarcoma metastasis model, kt-3283 prevented metastatic cancer growth in the lungs of mice inoculated with an aggressive Ewing’s sarcoma cell line.

“These results provide proof-of-concept for a novel single-molecule PARP-HDAC inhibitor in the treatment of Ewing’s sarcoma,” said Mads Daugaard Rakovina Therapeutics’ President and Chief Scientific Officer. “This concept is likely to be relevant for other cancer indications besides Ewing’s sarcoma, and may offer an opportunity to reduce resistance to PARP inhibitor therapy.”

The development of Rakovina Therapeutics’ novel kt-3000 DNA damage response inhibitor was awarded a St. Baldrick’s Foundation Martha’s BEST Grant for All to develop a new treatment for Ewing’s sarcoma, an aggressive bone and soft tissue cancer. Partially supported by in children and young adults.

About Rakovina Therapeutics Inc.

Rakovina Therapeutics Inc. is focused on developing new cancer treatments based on novel DNA damage response (DDR) technologies. The Company is pursuing new DNA clinical trials with the goal of advancing one or more drug candidates into human clinical trials and obtaining marketing approval for new cancer therapeutics from Health Canada, the U.S. Food and Drug Administration, and similar international regulations. We have established a pipeline of damage response inhibitors. agency. For more information, visit his website at: www.rakovinatherapeutics.com.

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