Cellceutix Corporation , a clinical stage biopharmaceutical company developing innovative therapies with dermatology, oncology, anti-inflammatory, and antibiotic applications, is pleased to update shareholders on continuing efforts to develop the oral dosing of Kevetrin.
Based on positive results from Cellceutix’s Phase 1 trial of Kevetrin in solid tumors conducted at Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, the Company is moving forward with a Phase 2 trial of intravenously-administered Kevetrin in patients with late-stage, platinum-resistant ovarian cancer. Cellceutix has decided to pursue an oral formulation for Kevetrin to improve patient convenience and potentially increase therapeutic efficacy given the drug’s short half-life and other pharmacokinetics, as discussed below.
As background, pre-clinical work determined the bioavailability of Kevetrin was 79 percent when given orally in Sprague-Dawley rats. To further establish the efficacy of oral Kevetrin, in vivo mouse studies were carried out in an ascites ovarian tumor model using OVCAR-3 and OV-90 tumor models, both of which possess different mutant p53 genes. Importantly, these pre-clinical results showed that the overall efficacy of Kevetrin was similar across both oral and intraperitoneal routes of drug administration.
Cellceutix has initiated a series of GLP (Good Laboratory Practice) studies to assess the safety of Kevetrin given orally. Considering that Kevetrin is a non-cytotoxic drug, our intent, with FDA permission, is to next proceed with a Phase 1 clinical trial in healthy volunteers using the oral route. These studies are being conducted by approved vendors and include: photosafety testing, pharmacokinetics, in vivo metabolism, metabolic stability, protein binding, and genetic and physiological toxicology reports.
Preliminary data analyses in a pharmacokinetic study in rats revealed a half-life of approximately 1 hour and a clearance of 78ml/min/kg for both oral and intravenous (IV) dosing. Results of an initial photosafety study demonstrated a molar extinction coefficient value of less than 5 L/mol*cm over a range of wavelengths above 290 nm, well below the 1000 L/mol*cm limit stated in ICH guidelines—indicating Kevetrin has no phototoxicity. A preliminary toxicity study showed that at doses up to 500 mg/kg given orally daily for 7 days, Kevetrin was well-tolerated by the rats as indicated by an 11 percent increase in body weight and no abnormal clinical observations. Further, this dose was greater than the doses used in the preclinical efficacy study. Remaining safety studies will be completed in the second half of this year.
In related news: Last week, Cellceutix research partners in Italy shared results with the Company from their ongoing preclinical work evaluating Kevetrin in Acute Myeloid Leukemia (AML), Pancreatic Cancer and human Gliobastoma Multiforme (hGBM). The data will be presented (by them) at scientific conferences, and is consistent with, and further informs, our knowledge of Kevetrin. Also, efficacy data from the 2nd cohort in the Brilacidin-Ulcerative Colitis proof-of-concept study is in the last stage of being compiled by the CRO and, following a final review, will be released.
Kevetrin is a small molecule that has demonstrated the potential of becoming a breakthrough cancer treatment by inducing activation of p53, a protein frequently referred to as the “Guardian of the Genome” due to its critical role in controlling cell mutations. In the majority of cancers, and regardless of origin, type, and location, the p53 pathway is mutated, preventing the body from performing its natural anti-tumor functions. Conducted at Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, a Phase 1 clinical trial evaluating Kevetrin in treating advanced solid tumors has been successfully completed, with patients showing good toleration and encouraging signs of potential therapeutic response. Cellceutix has initiated a Phase 2a trial of Kevetrin in platinum-resistant/refractory ovarian cancer. Patients will receive more frequent dosing (3 times per week) at higher levels and then receive standard of care treatment. Efforts also are underway to develop Kevetrin as an oral anti-cancer agent that can be administered daily, potentially even multiple times per day. The FDA has awarded Kevetrin Orphan Drug status for ovarian cancer, pancreatic cancer, and retinoblastoma, qualifying it for developmental incentives and a potential extra 7 years of market exclusivity upon drug approval. The FDA also has granted Kevetrin Rare Pediatric Disease designation for childhood retinoblastoma.
About Cellceutix Phase 2a Ovarian Cancer Trial Design
CTIX-KEV-201 is an open-label, Phase 2a study evaluating the safety, tolerability, and pharmacokinetics of Kevetrin as well as changes in select biomarkers and objective tumor response when administered to patients with platinum-resistant/refractory ovarian cancer. The clinical trial comprises two different short-term treatment regimens and will enroll an estimated 10 patients. Primary outcome measures include the incidence of Treatment-Emergent Adverse Events (TEAEs) and changes in pre-specified biomarkers (via tumor biopsy, examination of ascites fluid and peripheral blood), pre-treatment and post-treatment, at 3 weeks. Secondary outcome measures include objective tumor response, per Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) and plasma concentrations of Kevetrin.