BEVERLY, MA–(Marketwired – Apr 21, 2015) – Cellceutix Corporation (OTC: CTIX) (the “Company”), a clinical stage biopharmaceutical company developing innovative therapies with oncology, dermatology, and antimicrobial applications, is pleased to provide shareholders with a comprehensive update on current corporate activity and pipeline development.
Kevetrin – Refractory Solid Tumors
We began our first-in-human study of Kevetrin in patients with solid tumors in late 2012. At the beginning of April 2015, a total of 39 patients had received multiple doses of Kevetrin. We have found Kevetrin to be extremely well-tolerated, including the recently treated patients who received 450 mg/m2 — the highest dose yet administered. Laboratory experiments have shown Kevetrin acts by reactivating the key tumor suppressor protein p53, often called the “Guardian Angel Gene,” which is nearly always mutated or ineffective in cancer patients. The p53 target has long been a key focus in oncology research, although with limited success due to toxicity problems of candidate drugs. Kevetrin is potentially a breakthrough drug due to its mechanism of action and its safety profile.
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.
The protocol safety committee met on April 13, 2015 to review data for patients treated in the 450 mg/m2 cohort and recommended that the next cohort receive Kevetrin doses of 750 mg/m2 (a 67% increase in dose and 75x the initial dose).
The current protocol was originally designed to evaluate 40 patients. 39 patients have been treated to date, meaning that one patient will receive the 750 mg/m2 to complete enrollment per the original trial design. 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 late April or early May.
We intend to complete this trial in the coming months and initiate a follow on trial later in 2015 evaluating multiple weekly dose regimens of Kevetrin. The data that we have to date lead us to be very optimistic about the potential for Kevetrin.
Kevetrin- Acute Myelogenous Leukemia
We have previously announced that Kevetrin will be studied in a trial being sponsored by the University of Bologna and its European partners. The initiation of this trial was intentionally delayed pending further evaluation of Kevetrin dosing in our ongoing Phase 1 study. We are pleased to report we have been notified that based upon the data from the Phase 1 study, the original protocol has been revised and expanded from what was originally planned to be a Phase 1b study into a Phase 2 trial evaluating Kevetrin as a single agent or in combination with cytarabine in patients with Acute Myelogenous Leukemia (AML). Over 100 patients are expected to be enrolled in the trial. The new protocol will be submitted in May by the principal investigator at the University of Bologna to the institutional committee. This is an important trial for Kevetrin as these AML patients will be receiving Kevetrin on multiple consecutive days, which we believe will increase p53 activity. The primary objective of this trial is to evaluate the rate of complete remission of AML in patients receiving Kevetrin alone or in combination with cytarabine. We believe that if the trial shows clinical activity of Kevetrin or Kevetrin plus cytarabine in the treatment of AML, a disease that the American Cancer Society estimates accounts for 20,830 new cases and 10,460 deaths annually in the United States, we will see a substantial rise in interest in Kevetrin for potential use in leukemias.
Kevetrin- Renal Cancers
We have also discussed plans for Kevetrin to be independently studied by investigators at Beth Israel Deaconess Medical Center (BIDMC) in combination with a tyrosine kinase inhibitor as a potential new combination therapy for renal cancer, a tumor that is particularly resistant to therapy. In its research, BIDMC has noted in vivo tumor regression in a drug-resistant renal cancer cell line exposed to the combination of Kevetrin and sunitinib. We have previously supplied BIDMC requested information to investigate a Specialized Programs of Research Excellence (SPORE) grant. It is hopeful these plans will progress to the initiation of a multicenter Phase 2 clinical study of Kevetrin in combination with a tyrosine kinase inhibitor.
Brilacidin – Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
We are developing Brilacidin under a Qualified Infectious Disease Product (QIDP) designation from the FDA as a potential new and unique treatment for ABSSSI. In our completed 215-patient Phase 2b trial of Brilacidin ABSSSI, two different single dose treatments of Brilacidin, as well as a three-day regimen, were all shown to be comparably effective as the FDA-approved 7-day dosing regimen of the blockbuster antibiotic daptomycin. In 2014, daptomycin was marketed under that brand name Cubicin by Cubist Pharmaceuticals and generated $1.046 billion in sales. In December 2014, Merck & Co. agreed to acquire Cubist Pharmaceuticals for approximately $9.5 billion, including debt.
We released the positive top-line data from the Phase 2b Brilacidin trial in October 2014. After our initial submission of data from this study to the FDA, the agency requested additional data from the trial. We have gathered microbiologic (MIC) data from bacterial pathogens isolated in the trial, analyzed pharmacokinetic (PK) data, performed pharmacodynamic (PD) modeling, and conducted in-depth evaluations of the safety profile of Brilacidin in comparison to daptomycin in this patient population. We anticipate meeting with the FDA for an End-of-Phase 2 meeting in late June 2015. Upon the FDA accepting our proposals, we will commence Phase 3 trials of Brilacidin for ABSSSI.
Brilacidin – Prevention or Attenuation of Oral Mucositis in Head and Neck Cancer
We are conducting a Phase 2 trial of Brilacidin oral rinse for the prevention or attenuation of oral mucositis (OM), a common and often debilitating inflammation and ulceration condition that occurs in the mouth as a side effect of chemotherapy and radiation therapy for head and neck cancer. Approximately 450,000 patients each year in the United States experience OM, which affects the course and outcome of cancer therapy. Pre-clinical studies in an animal model indicate that the antibacterial, anti-biofilm and anti-inflammatory properties of Brilacidin can potentially provide a strong therapeutic benefit to OM patients. The FDA accepted our Investigational New Drug application in October 2014 to begin the trial. Since that time, we made modifications to target specific investigator sites having significant experience in conduct of this type of study and ultimately doubled the original number of planned sites to expedite recruitment. We expect subject enrollment in this trial to commence in May. OM represents a great area of unmet medical need and is potentially a very important and valuable asset in the Brilacidin development pathway.
Brilacidin- Ulcerative Proctitis / Colitis
We have also identified gastrointestinal (GI) disease as an indication for treatment with Brilacidin. We are now reviewing our clinical strategy and at this time plan to advance a topical version of Brilacidin into a European Phase 2 trial to evaluate Brilacidin in the remission of ulcerative proctitis, an idiopathic mucosal inflammatory disease and a form of ulcerative colitis involving only the rectum or the distal colon and rectum (proctosigmoiditis). We hope to initiate a Phase 2 trial in 2015 to expand into the lucrative GI markets, with the potential for additional trials targeting ulcerative colitis, Crohn’s Disease and other conditions where today’s treatment options are very limited in effectiveness.
Prurisol – Plaque Psoriasis
We are developing our oral anti-psoriasis drug Prurisol under FDA guidance that Prurisol will be eligible for a 505(b)(2) drug approval pathway because the active moiety of Prurisol (abacavir) is the same as that of the marketed drug Ziagen® (abacavir sulfate). A murine xenograft model with human psoriatic tissue has shown robust activity of Prurisol in resolution of all signs of psoriasis without reoccurrence. Following FDA guidance for the expedited 505(b)(2) pathway, we completed a Phase 1 crossover trial successfully demonstrating that Prurisol converts to abacavir in healthy humans. During our end-of-Phase 1 meeting with the FDA, we were advised that, pending full review of the Phase 1 data, long-term safety data for Prurisol in the treatment of psoriasis would not be required, as the long-term safety data of Ziagen® can be referenced. In December, the FDA gave us permission to begin a Phase 2 trial of Prurisol for psoriasis. Subsequently, we have completed GMP manufacturing of Prurisol and placebo, engaged vendors and principal investigators and contracted with sites to begin the trial. We expect enrollment to begin in 2Q 2015. We are engaging the trial at more clinical sites than originally planned and expect to make up for lost time as the manufacturing process took longer then expected. Given that psoriasis is a chronic condition with limited effective therapies that the National Psoriasis Foundation lists as affecting 125 million people worldwide, we see a tremendous market opportunity for an effective new oral treatment. We expect enrollment in this study to be completed during 2015.
We also plan to conduct a Phase 2 clinical trial of topical version of one of our HDP mimetic compounds for the treatment of hidradenitis suppurativa (HS). Also known as acne inversa, HS is a chronic and debilitating inflammatory skin disease characterized by recurrent abscesses and formation of sinus tracts, typically where skin rubs together, such as the armpits, groin, between the buttocks and under the breasts. First described 176 years ago, there still is no cure and only limited effective treatment options. Reports of prevalence range widely from approximately one-half a percent up to approximately four percent of the general population. HS presents in many forms, with a number of hard-to-treat bacterial species commonly isolated in HS lesions; bacteria that studies show our novel compounds to be active against. After careful consideration, we have now cancelled a scheduled May pre-IND meeting with the FDA to discuss initiating a Phase 2 trial for HS. We believe it is a more prudent use of resources to expand upon on our more advanced compounds at this time. After the start of our other Phase 2 trials, and as we can devote more resources specifically to an HS therapy, we will return to advancing this project toward the clinic.
Elsewhere in our extensive pipeline, we and/or our partners have conducted very promising research that supports additional clinical trials that we plan to focus on in the future. Namely, we are developing formulations for ophthalmic, otic and diabetic foot infections. We have a growing body of evidence to the potential efficacy of our HDP mimetic compounds for the treatment of Gram-negative bacteria and fungal pathogens. In light of the awareness and government initiatives to develop new drugs to stop so-called “superbugs” that are resistant to most or all of today’s therapies, compounds addressing multi-drug resistant bacterial and fungal diseases and conditions are extremely valuable and of high profile today. We have disclosed that research, much of which is conducted under government grants at a major university in Texas and by Fox Chase Chemical Diversity Center. These studies show that our HDP mimetics are active with low toxicity against some of today’s most problematic pathogens, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Acinetobacter baumannii, as well as highly multi-drug resistant ndm-1-producing Klebsiella pneumoniae. Lab research on CTIX-1502, one of our early lead compounds, has shown it to be active against systemic and localized Candida infections, including being comparable or superior to the commonly used topical anti-fungal agent nystatin in an oral candidiasis mouse model. With respect to these different indications, we are manufacturing compounds as GMP material and intend to move forward to initiate a broad Phase 1 trial to define which indications are best targeted.
European Congress of Clinical Microbiology and Infectious Diseases
Cellceutix will have three presentations highlighting its novel antibiotics at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) to be held in Copenhagen, Denmark from April 25 – April 28, 2015. ECCMID is one of the largest annual gatherings of infectious disease experts in the world.
A presentation of results in the phase 2b clinical trial “A randomized, double-blind study comparing single-dose and short-course brilacidin to daptomycin in the treatment of acute bacterial skin & skin structure infections (ABSSSI)” will be given in an oral presentation at 4 pm on April 27, 2015. A second oral presentation entitled Synthetic Novel Host Defense Protein mimetics for the treatment of Gram-negative bacterial infections will be given at 2:30 pm on April 26, 2015. A poster presentation entitled Brilacidin, Host Defense Peptide mimetic, one of a new class of immunomodulatory agents that can target multiple disease indications, will be on display all 4 days of the conference.
Our NASDAQ application is in process. We made our selections and now received confirmation of acceptance of positions for new members to the Company’s Board of Directors and committees required to move to the NASDAQ exchange. This information has been prepared in the form of an 8-K filing for submission to the Securities and Exchange Commission (SEC) and is currently being reviewed by our SEC counsel. Under guidance of our legal counsel, we will be publicly releasing this information simultaneously with the 8-K submission.
“There are many exciting developments ongoing at Cellceutix, both at the corporate level and from a drug development perspective,” commented Leo Ehrlich, Chief Executive Officer at Cellceutix. ”We have always held that the best approach to build shareholder value is to conduct multiple projects concurrently. We are executing efficiently at this business model, targeting large markets with novel drugs, while running a lean operation. In a relatively short period of time, we have grown exponentially and will soon have several Phase 2 trials and a Phase 3 study happening as we stand in the best financial position in the Company’s history.”