BEVERLY, MA–(Marketwired – November 10, 2015) - Cellceutix Corporation (OTC: CTIX) (the “Company”), a clinical stage biopharmaceutical company developing innovative therapies with oncology, dermatology, anti-inflammatory and antibiotic applications, has filed its quarterly report on Form 10-Q for the quarter ended September 30, 2015 with the Securities and Exchange Commission. A copy of the report is available to be viewed or downloaded on the Company’s website.
Cellceutix is now in four clinical programs and we have a number of development programs. Our clinical trials are listed on our website and onwww.clinicaltrials.gov.
We are not a “me too” company, not a one product, or even a one technology company. Our four clinical trials involve three very different compounds, including Kevetrin and Brilacidin, two novel compounds never before seen in medicine. The two trials using Brilacidin are for completely different uses of this very promising compound. One is for its abilities as an antibiotic now proven in hundreds of patients and the other is as an anti-inflammatory, now in a Phase 2 trial for treating oral mucositis. Successes with these compounds open up boundless possibilities and opportunities. Our compounds are advancing in clinical trials addressing major patient populations and those in need of more effective and safe therapies.
Kevetrin, our lead anti-cancer drug
On Monday, November 9, 2015, the sixth qualifying patient in the present cohort received their third Kevetrin treatment at 750 mg/m2. To wit, enrollment in the Kevetrin Phase 1 clinical trial is now closed to new subjects. The decision to formally conclude the trial will now be reviewed by the Company and Principal Investigator.
Kevetrin, our anti-cancer compound, is being studied in a Phase 1 trial at Dana-Farber Cancer Institute and 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 trial is evaluating Kevetrin under the most challenging of situations, treating late-stage, advanced solid tumor cancer patients that have exhausted other treatment options without success. The primary endpoints for the study are safety, determining the maximum tolerated dose, and establishing the dose for future Phase 2 clinical trials.
Exposure to Kevetrin as measured by plasma concentrations have been achieved which are greater than concentrations shown to induce apoptosis in non-clinical studies. 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.
Enough data has been collected in the Phase 1 study for now advancing Kevetrin to a Phase 2 clinical trial. This data is being used to design the Kevetrin dosing regimen in the planned studies of patients with advanced ovarian carcinoma. An FDA meeting request had been submitted in the last week of October 2015. Subject to FDA guidance and authorization, the Company plans a multi-arm study evaluating Kevetrin as a mono-therapy and as a component of a combination therapy. To date, pharmacokinetic profiles found that the plasma half-life of Kevetrin is relatively short, supporting the projected administration of multiple infusions each week in the next study. The half-lives after the first dose and after the sixth dose do not differ appreciably. Longer durations of Kevetrin infusion have shown prolonged exposure to the drug. Prolonged exposure and high area-under-the-curve (AUC) may be desirable in therapy of solid tumors especially with Kevetrin since activation of cell death signaling requires multiple gene synthesis and the phase or phases of the tumor cell cycle most susceptible to the effect(s) of Kevetrin is not known.
Kevetrin was granted FDA Orphan Drug Designation for the treatment of ovarian cancer.
In August 2015 an application was submitted to the FDA requesting a Rare Disease Designation for Kevetrin for the treatment of pediatric retinoblastoma. We are awaiting a response from the Agency.
We are pleased to report that we have submitted our first paper on Kevetrin and p53 for peer-review and publication at a relevant scientific journal. Now that significant clinical data has been collected on Kevetrin, it’s time for us to begin publishing in peer-reviewed journals to complement the peer-reviewed data presented at oncology conferences. We believe that publications in scientific/medical journals will attract more attention towards Cellceutix and benefit our shareholders.
Prurisol – Plaque Psoriasis
In August 2015, we commenced a Phase 2 trial of Prurisol, an orally administered small molecule for the treatment of plaque psoriasis. We are developing Prurisol under FDA guidance that a 505(b)(2) drug approval pathway is an acceptable pathway for its development. This offers the benefits of a faster development process. Prurisol was eligible because its active moiety of 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. 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. As previously reported, we expect to complete enrollment by year end 2015.
Brilacidin – Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
The intravenous formulation of our lead antibiotic candidate, Brilacidin, has the potential to treat a variety of infections, including Acute Bacterial Skin and Skin Structure Infections (“ABSSSI”), caused by drug-sensitive or drug-resistant strains of Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA), and by other Gram-positive bacteria.
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. In April 2015, safety and efficacy results from this 215-patient study of brilacidin in patients with ABSSSI, were presented at the 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). In addition, population pharmacokinetic data from this study were presented in a poster at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in San Diego in September 2015.
In July 2015, at an End-of-Phase 2 Meeting, Cellceutix and FDA discussed data supporting advancement of brilacidin into Phase 3, as well as the basic elements of a Phase 3 program in ABSSSI. This is the first Host Defense Protein (HDP) mimic to advance through Phase 2. Because HDP mimics, such as brilacidin, represent an entirely new class of antibiotics, there is no potential cross-resistance with currently marketed antibiotics, and due to its unique mechanism of action, resistance to brilacidin is unlikely to develop. For this and other reasons, such as its high activity against methicillin-resistant Staphylococcus aureus (a leading cause of ABSSSI) brilacidin received designation as a Qualified Infectious Disease Product (QIDP) in November 2014. The QIDP designation was established as part of the Generating Antibiotic Incentives Now (GAIN) Act, passed by the U.S. Congress in July 2012, for the purpose of encouraging pharmaceutical companies to develop new antimicrobial drugs to treat serious and life-threatening infections. Receiving QIDP designation means that Brilacidin is now eligible for additional FDA incentives in the approval and marketing path, including Fast Track designation and Priority Review for development and a five-year extension of market exclusivity.
The Phase 3 ABSSSI program would include two Phase 3 ABSSSI studies, as required by FDA Guidance (October 2013), of approximately 700 subjects in each study. The two studies may enroll subjects simultaneously. In addition, the first study would include an interim analysis after a portion of the patients has been enrolled. This would provide an early assessment of both safety and efficacy.
The Company is now engaged in activities necessary for beginning the Phase 3 study. In September 2015, Cellceutix submitted its initial Pediatric Study Plan (PSP) to the Food and Drug Administration (FDA) for the use of Brilacidin IV in the treatment of ABSSSI in children. Cellceutix agreed to submit the PSP during its end-of-phase 2 meeting with FDA in mid-July. The submission of the PSP is the first of many requirements in expanding the use of brilacidin to children.
Although phase 3 start up activities may take a little longer than usual for a new class of compounds, the Company remains on track in its preparations.
The Company has produced large quantities of brilacidin for the phase 3 program and in the coming weeks, we will be completing our laboratory testing on this newly manufactured compound. To date these lots have passed our standards for quality controls. In addition, the Company has completed its interviews of Contract Research Organizations (CROs) that have experience conducting global phase 3 ABSSSI studies.
It has been decades since a new class of antibiotics has made it to phase 3. Brilacidin is unique in its structure and function. As an antibiotic, it is can kill bacteria that are resistant to other antibiotics, such as methicillin-resistant Staphylococcus aureus (MRSA), a major cause of ABSSSI. And we believe that resistance to brilacidin is unlikely to occur. As for brilacidin’s immunomodulatory activity, we are just scratching the surface.
Although ABSSI may appear to be a crowded space, the Company believes that brilacidin has several advantages over existing ABSSSI therapies. These include:
1. It can be given as a single IV dose. At present, there is only one approved drug — and no generics — that can be given a single time for treating ABSSSI.
2. As the first in a new class of antibiotics known as Host Defense Protein (HDP) mimics, there is no expected cross-resistance. In contrast, all of the newly approved ABSSSI drugs have come from existing classes of antibiotics that have been marketed for years, if not decades. This means resistance has already developed to older members of that class, and when bacteria are exposed to the new members of the same class, cross-resistance is likely to occur.
3. Brilacidin is also effective against the stationary phase of bacteria. Most bactericidal antibiotics require bacteria to be in an “active growth phase” in order for rapid killing to occur. However, brilacidin is active against bacteria in both the rapid growth phase and the stationary phase, and it has been shown to disrupt biofilms. This means that brilacidin, unlike other ABSSI drugs, has the potential to be used for biofilm-related infections caused by Staph aureus. In addition, by killing bacteria in both phases (rapid growth and stationary), this decreases the opportunity for a “persistent bacteria” to evolve into a “resistant bacteria.” This is yet another way that brilacidin could reduce the burden of resistance.
4. Brilacidin has immunomodulatory activity, including anti-inflammatory activity. This is not surprising, as brilacidin was created to mimic the molecules (HDPs) that comprise our innate immune system. This is the immune system that protects our barriers surfaces, such as skin and mucous membranes. These immunomodulatory properties may help accelerate the healing of infections. In addition, these properties allow us to use brilacidin for inflammatory conditions. For example, brilacidin is in a phase 2 study as an oral rinse for the prevention of oral mucositis in patients undergoing chemoradiation for head and neck cancer.
Brilacidin for Oral Mucositis (OM)
In animal models of oral mucositis induced by chemoradiation, topically applied Brilacidin was shown to significantly reduce the occurrence of severe ulcerative oral mucositis by more than 90% compared to placebo. Brilacidin and related compounds have shown antibacterial, anti-biofilm and anti-inflammatory properties in various pre-clinical studies. We believe that the combination of these attributes contributed to the efficacy of Brilacidin in these animal studies.
The Company is engaged in a clinical trial titled a “Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Brilacidin Oral Rinse Administered Daily for 7 Weeks in Attenuating Oral Mucositis in Patients with Head and Neck Cancer Receiving Concurrent Chemotherapy and Radiotherapy”. Recruitment is ongoing and the Company is continually looking to add additional study sites to quicken the completion of the trial.
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 and Hidradenitis Suppurativa
We have also identified inflammatory gastrointestinal disease (ulcerative proctitis) and inflammatory skin disease (hidradenitis suppurativa) as indications for treatment with Brilacidin or our other HDP mimics. The Company is preparing to advance these programs upon review of preliminary results in the oral mucositis trial.
Brilacidin for Topical Applications and Otic Infections and Related Formulation Work
Cellceutix is formulating and conducting preclinical experiments on topical Brilacidin for use in topical skin applications such as diabetic foot ulcer infections, and for ear-related infections, such as otitis externa or draining otitis media. On July 14, 2014, the Company announced that a significant breakthrough had been made in the formulation of Brilacidin. Previously, Brilacidin was stored in a refrigerated state. The Company has now developed the formulation of Brilacidin to be stable at room temperature. However, further formulation work is still needed for each indication. Upon developing optimal formulations, the Company plans to advance these drugs into the clinic. The Company believes this work, though challenging, is very important.
Advancing the Platform and Developing Compounds with Activity Against Gram-Negative Bacteria and Fungi
Also in our antibiotic/antifungal portfolio, we are actively testing several of our compounds both in house and through research grants at major universities. In the Gram-negative program, our lead compounds are active in laboratory testing against some of the most problematic pathogens, such as Pseudomonas, Klebsiella, E. coli and Acinetobacter. We have compounds active against drug-susceptible strains as well as multi-drug resistant strains that produce Klebsiella pneumoniae carbapenamase (KPC). These are also called carbapenem-resistantEnterobacteriaceae (CRE). CRE has been identified by the Centers for Disease Control (CDC) as an “urgent threat” to public health. Importantly, several of our compounds have been shown to be active against CRE in the laboratory. These results were reported in an oral presentation at the European Society of Clinical Microbiology and Infectious Diseases (ECCMID) in Copenhagen in May 2015.
In our anti-fungal program, we have identified a series of HDP mimics that are highly active against Candida species and exhibit very low cytotoxicity against mammalian cell types. Last year, we announced our collaboration with Fox Chase Chemical Diversity Center, which led to the award of a $1.5 million Phase 2B Small Business Innovation Research (SBIR) Grant. Laboratory experiments have shown that, like the antibacterial HDP mimics, the potential for resistance development by Candida is very low. Early studies have delivered promising results in mouse models of Candida in both topical and systemic applications. Additional studies of our HDP mimics suggest possible new treatments for other fungal pathogens, including Aspergillus strains.
In addition to their antimicrobial activity, we are evaluating the use of current and future host defense protein (HDP) mimics for disorders of barrier function, where the innate immune system plays a vital role. For these disorders, the goal is to exploit the anti-inflammatory and anti-biofilm properties to restore and maintain healthy skin and mucous membranes, and to treat refractory biofilm-related infections on natural and artificial surfaces. This would include inflammatory or trauma-related conditions of the skin, eyes, GI tract, and respiratory mucosa; exacerbations of chronic bronchitis and cystic fibrosis; and infections of catheters, valves, and prosthetic joints.
Cellceutix also wishes to inform shareholders that a proxy statement has been filed with the Securities and Exchange Commission for the Company’s first Annual General Meeting of Shareholders. The meeting, scheduled for 10 AM ET, Tuesday, December 15, 2015 at 100 Cummings Center, Suite 221-E, Beverly, Massachusetts, will give us an opportunity to meet shareholders and select auditors and discuss corporate matters.
As you can see, this is an exciting and productive time for the Company. We look forward to sharing information on all of our clinical research in future updates.