On April 20, 2023 Edison Oncology Holding Corp. ("Edison Oncology"), a privately held biopharmaceutical company, reported the presentation of two scientific posters at the annual meeting of the American Association of Cancer Research held in Orlando, Florida from April 14-19 (Press release, Edison Oncology, APR 20, 2023, View Source [SID1234630365]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
In a presentation entitled "A Pilot Clinical Trial of VAL-413 (Orotecan, oral irinotecan HCl) in Patients with Recurrent Pediatric Solid Tumors," the company reported that, to date in its ongoing Phase 1-2a clinical trial, of Orotecan, a novel oral formulation of irinotecan, no dose limiting toxicity has been observed in patients receiving Orotecan, and preliminary analysis of pharmacokinetic data suggests that plasma levels of irinotecan and its active metabolite, SN-38, are similar to levels observed following treatment with unformulated commercially available i.v. irinotecan given orally in the same patient.
In a second presentation entitled "Investigating the Therapeutic Efficacy of EO3001 in Clear Cell Carcinoma of the Ovary", Edison Oncology reported that in CRISPR/Cas9 generated isogenic pairs of ovarian cancer cell lines, EO3001 selectively kills ARID1A mutant cancer cells at low nanomolar concentrations compared to "wildtype" ovarian cancer cells that do not harbor the mutation. A mechanism of action of EO3001 in ARID1A mutant ovarian clear cell carcinoma (OCCC) is also proposed. Since ARID1A mutations are known to inactivate the SWI/SNF complex and expose the DNA into an "open chromatin" structure, such cells have high DNA replication and enhanced metabolic rates. To meet this enhanced energy need such cells become dependent on oxidative phosphorylation (OXPHOS). The poster describes that by directly inhibiting the action of certain mitochondrial proteins required for the function of the OXPHOS pathway, EO3001 may result in energy deprivation and apoptosis the of metabolically overactive ARID1A mutant tumor cells.
About Orotecan (oral irinotecan HCl)
Orotecan is a novel oral liquid formulation of irinotecan hydrochloride designed to deliver the drug orally with improved tolerability. Irinotecan is an intravenous (i.v.) topoisomerase inhibitor approved by the FDA for the treatment of colorectal cancer and used ‘off label’ in the treatment of a several types of cancer including gastric cancers, neuroendocrine and adrenal tumors, pancreatic cancer, small cell lung cancer, cervical cancer, ovarian cancer, esophageal cancer, soft tissue sarcomas and bone cancer.
A standard regimen of i.v. irinotecan for the treatment of childhood tumors involves daily infusions for five consecutive days, every two to three weeks leading to significant patient inconvenience, diminished quality of life and high cost to the healthcare system. "Orotecan’s oral formulation has been developed to improve tolerability and patient compliance in the treatment of rare childhood tumors, with an opportunity to expand into major adult cancers," said Jeffrey Bacha, Edison Oncology’s chief executive officer.
"The data we have observed in our clinical trial thus far supports our confidence that Orotecan has the opportunity to address significant unmet needs in a number of tumors where i.v. irinotecan is currently utilized as a single agent, or in combination with oral anti-cancer treatments."
To date, more than 200 patients have been treated with unformulated commercially available i.v. irinotecan delivered orally with promising results in the treatment of Ewing sarcoma and other pediatric cancers; however, poor palatability of the drug has limited the widespread adoption of this approach in clinical practice.
Edison Oncology’s ongoing clinical trial (clinicaltrials.gov identifier: NCT04337177) is designed to examine the safety and tolerability of Orotecan and provide data assess the pharmacokinetics of Orotecan compared to current oral regimen employing unformulated i.v. irinotecan given orally.
About EO3001
EO3001 is a novel small-molecule drug candidate that has been studied in prior clinical trials involving more than 1000 patients. Recent research conducted by Edison Oncology and academic researchers has demonstrated EO3001 exhibits potent and selective activity against ARID1A deficient cancer cells. Mutations in ARID1A are associated with treatment resistance and poor outcomes in several cancers including gynecologic malignancies, breast cancer, gastric cancer, colorectal cancer and pancreatic cancer.
Ovarian clear cell carcinoma (OCCC) is an orphan cancer indication representing approximately 10% of ovarian cancers in North America with a higher frequency in patients of east Asian descent. OCCC is inherently resistant to standard chemotherapy and radiation treatment and currently represents the worst prognosis of any form of epithelial ovarian cancer.
"According to published studies up to 60% of OCCC patients harbor ARID1-A mutations, providing a readily available biomarker for patient selection in clinical trials," said Mr. Bacha. "We look forward to advancing EO3001 as a potential treatment for this important unmet medical need."