Del 10Q que CTIX publicó ayer...
Kevetrin, our novel anti-cancer compound, has demonstrated the potential for a major breakthrough in cancer research by exhibiting an activation of wild type p53 and degradation of mutant p53. Tumor protein p53, often referred to as the “Guardian Angel Gene” or the “Guardian Angel of the Human Genome” due its crucial role in controlling cell mutations, is a tumor suppressor protein that is encoded by the TP53 gene in humans and has been widely regarded as possibly holding a key to the future of cancer therapies. Additional studies have shown that Kevetrin has potent anticancer activity in a wide range of tumor types by targeting histonedeacetylase (HDAC).
The Phase 1 trial for Kevetrin is being conducted at Harvard Cancer Center's Dana-Farber Cancer Institute and its partner institution Beth Israel Deaconess Medical Center. The clinical trial is evaluating the safety and potential efficacy of Kevetrin in patients with advanced-stage solid tumors of various types. The primary endpoints for the study are safety, determining the maximum tolerated dose and establishing the dose for a future Phase 2 clinical trials.
At the beginning of May 2015, a total of 40 patients had received Kevetrin. We have found Kevetrin to be extremely well-tolerated, including in one patient who received their first treatment at 750 mg/m2 – the highest dose yet administered and is 75x the initial study dose.
The current protocol was originally designed to evaluate 40 patients and we have now reached the limit without concluding the trial. Because of the stepwise increases in Kevetrin dose that have occurred, and the fact that a maximum tolerated dose has not been identified, Cellceutix has requested amendment of the protocol to allow treatment of additional patients at higher doses of Kevetrin. The Company has been advised that this request has been scheduled for the next Institutional Review Board meeting in May.
While the trial is primarily to evaluate safety of repeated cycles of Kevetrin, it is encouraging that some patients have had stabilization of tumor status during treatment. Further, Kevetrin appears to be having the expected effects on p53 in a number of the patients treated, as measured by increases in the levels of the downstream protein p21 biomarker. According to the latest data, over 50% of patients treated have had increases in the p21 marker. In addition, the effect on p53/p21 appears to be dose-dependent, with patients treated in the cohorts receiving 350 and 450 mg/m2 of Kevetrin showing greater increases in levels of p21. At this time, the Company is saving the full p21 results for an appropriate scientific venue.
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The Phase 2b trial entitled “A Randomized, Double-Blind Study Comparing Three Dosing Regimens of Brilacidin to Daptomycin in the Treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSI)” completed enrollment in August 2014. On October 23, 2014, we announced positive top-line efficacy data from this Phase 2b ABSSSI trial, and on January 5, 2015, we reported the corresponding 95% confidence intervals.
The trial, which began in February 2014, enrolled 215 total subjects, with approximately 25% in each of the four treatment arms. The primary endpoint was clinical success, defined as reduction of at least 20% in area of ABSSSI lesion, relative to baseline, when observed 48-72 hours after the first dose of study drug, and no rescue antibiotics administered. This is consistent with the 2013 Food and Drug Administration (FDA) guidance for ABSSSI studies and is the same endpoint used in recent approvals for ABSSSI drugs.
In treated patients assessed at 48-72 hours, 47/51 (92.2%), 46/48 (95.8%), 51/52 (98.1%), and 45/48 (93.8%) achieved clinical success in the Brilacidin 0.6 mg/kg single-dose group, Brilacidin 0.8 mg/kg single-dose group, Brilacidin 1.2 mg/kg 3-day group, and daptomycin 7-day group, respectively. The corresponding 95% confidence intervals around the clinical success rates were 85-100%, 90-100%, 94-100%, and 87-100%, respectively. Although this Phase 2b study was not powered for statistical comparisons, the 95% confidence intervals overlap, which indicates similar efficacy across all treatment groups. All Brilacidin treatment regimens were well tolerated. There were six severe adverse events (SAE) reported across the study, none of which were considered related to Brilacidin by the principal investigator. The Company believes that the trial met the Company’s clinical goals and that Brilacidin shows the potential to be a first in class drug.
