VANCOUVER, British Columbia, April 20, 2023 (GLOBE NEWSWIRE) -- Rakovina Therapeutics Inc. (the “Company”) (TSXV:RKV) today announced the presentation of new data describing the progress of the Company’s kt-3000 drug development program at the American Association of Cancer Research (AACR) annual meeting in Orlando, Florida.
The Company’s data was presented in the DNA Damage Response section at the AACR annual meeting in a poster entitled “A novel bi-functional agent targeting PARP and HDAC in Ewing sarcoma”.
Ewing sarcoma is a highly aggressive bone and soft tissue tumor affecting mainly children and young adults, with a dismal 5-year survival rate of 15-30% for metastatic disease. Previous studies have demonstrated that Ewing sarcoma cells are sensitive to FDA-approved PARP inhibitors, but clinical trials have failed to produce a durable treatment response.
Rakovina Therapeutics' kt-3000 series is a novel class of DNA-damage response inhibitors with dual PARP HDAC inhibitor functionality.
The combination of a PARP inhibitor with an HDAC inhibitor have shown potential synergy in laboratory studies. However, the clinical treatment of patients with the combination to date has been associated with significant side effects, limiting the adoption of this therapeutic strategy.
The kt-3000 series was designed based on the hypothesis that combining both HDAC and PARP inhibition into a single molecule would provide a more viable approach to providing clinical benefit to patients, while retaining efficacy and limiting side effects.
Data presented at the meeting demonstrate that Rakovina Therapeutics' kt-3000 prototype lead candidate exhibits higher PARP-1 vs. PARP-2 selectivity compared to the FDA-approved PARP inhibitor, olaparib. Selectivity against PARP1 is believed to correlate with an improved safety profile vs. first-generation PARP inhibitors.
The data also demonstrate that the dual functional kt-3000 prototype lead candidate is more effective against Ewing sarcoma tumor cells than either a PARP inhibitor or HDAC inhibitor alone. This is achieved despite reduced potency at HDAC compared to the FDA-approved HDAC inhibitor, vorinostat.
The kt-3000 lead candidate effectively reduced lung metastases in mice inoculated with Ewing sarcoma tumor cells. The most common site where Ewing sarcoma metastasizes, or spreads, in patients is to their lungs, which is a leading cause of morbidity and mortality.
"The kt-3000 series compounds were designed with an aim of achieving synergistic PARP+HDAC activity against treatment of resistant tumors while improving safety and tolerability of treatment," said Prof. Mads Daugaard, Rakovina Therapeutics' president and chief scientific officer.
“We believe that this profile offers potential as a new treatment for tumors traditionally resistant to therapy, particularly in the recurrent disease setting for Ewing sarcoma and major cancers such as breast and ovarian cancer that has become resistant to treatment with FDA-approved PARP inhibitors," he added.
Select kt-3000 lead candidates are being evaluated for pharmacokinetics and safety in vivo as part of the process to select a primary lead candidate for advancement to human clinical trials.
About Rakovina Therapeutics Inc.
Rakovina Therapeutics Inc. is focused on the development of new cancer treatments based on novel DNA-damage response technologies. The Company has established a pipeline of DNA-damage response inhibitors 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 United States Food and Drug Administration and similar international regulatory agencies. Further information may be found at www.rakovinatherapeutics.com.
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