Cellceutix Announces Filing of its Annual Report on Form 10-K

BEVERLY, MA–(Marketwired – September 8, 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 Annual Report on Form 10-K for the year ended June 30, 2015 with the Securities and Exchange Commission.  A copy of the Annual Report is available to be viewed or downloaded on the Company’s website at: http://www.cellceutix.com/financials/.

In conjunction with the Annual Report, Cellceutix is pleased to release this announcement by Leo Ehrlich, CEO, and Dr. Daniel Jorgensen, Chief Medical Officer, providing an overview of the current developmental status of the Company’s pipeline of compounds.

On Friday, a lawsuit was filed based on an article posted by an anonymous writer on Seeking Article.  The article and the lawsuit have no merit and are filled with patently false information. We have sent an alert updating our shareholders and it’s available for viewing on our website.  We will vigorously defend our company, compounds and shareholders in this frivolous lawsuit with scientific evidence, rather than the unscientific prattle offered by this anonymous author. We encourage interested parties to learn the facts about Cellceutix and its drugs in development through due diligence in this overview and at other reputable sources.

We are now in four clinical programs and we have a number of development programs.  Our clinical trials are listed on our website and on www.clinicaltrials.gov.

Helping us in our operations, we rely on the depth of our 14 employees and the engagement of many brilliant consultants and vendors. Some of our consultants are key opinion leaders in their area of expertise in science and medicine.  For example, for our Gastrointestinal Disorder development program, our physician consultant is a department head at a major university hospital and the author of a popular book on the subject .

Cellceutix is a unique company.  We are a company devoted to only making drugs for unmet medical needs.  “Unmet medical needs” are important words in distinguishing our objectives.  The best way to explain this is with an example.  Let’s take a common situation: a pediatric ear infection.  A visit to the pediatrician or pediatric ENT can result with a prescription, for example the antibiotic Amoxicillin twice or three times a day for 10 days.  Now, if we wanted to compete with a drug that achieves the same results as Amoxicillan, but can be taken less frequent by a child, perhaps only a single dose, it would seem like a great idea for development.  But it’s not.  Insurance companies would likely dismiss the extra convenience and not reimburse for its use. Likely, they would only allow for using Amoxicillin, which is very inexpensive.  However, if the new drug fights a bacteria, such as MRSA, that the Amoxicillin doesn’t, you now have a potential winner because you’ve met an unmet medical need and the patient may need this. Drugs that address unmet medical needs have the best chances for attracting potential partners and increase the odds for insurance and Medicare reimbursement following approval, the ingredients for market success.

The very first analysis we do here at Cellceutix for every drug development program is ask the question, “Does it address an unmet medical need?”

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.

We will begin with discussing Kevetrin, our lead anti-cancer drug. We believe cancer drugs needn’t be poisons injected into people who are already suffering from cancer, which exacerbate the pain and further diminish quality of life. We believe cancer drugs can be far better then those presently approved. We have not accepted the conventional thinking and have created a whole new class of chemistry in medicine with Kevetrin.

As we have many new shareholders at Cellceutix, many things previously announced are worth repeating to provide a little framework and familiarity of what Kevetrin is all about.

Kevetrin is a novel drug now completing a Phase 1 Clinical trial. The trials are evaluating Kevetrin under the most challenging of situations, treating late-stage, advanced solid tumor cancer patients that have exhausted other treatment options without success.

In preparation for human trials, we dedicated years to pre-clinical research of Kevetrin to test our proprietary compound against many different cancer lines and delineate its Mechanism of Action (MOA).  What we discovered was potent anticancer activity against every type of cancer that we tested, even mutated cancers that were resistant to present day medications.  The data showed Kevetrin to be effective against lung, breast, colon, prostate, squamous cell carcinoma, a leukemia tumor model and malignant glioma.  In all of our research, tumor growth delay and tumor size reduction was shown.  These and other data have been presented at leading oncology conferences, including the American Association of Cancer Research recognizing early studies of Kevetrin as one of the “Frontiers” in cancer research because of its MOA and apparent low toxicity.

Kevetrin is not simply a cytotoxic, but a targeted non-genotoxic drug.

Now is the perfect time to give an overview of Kevetrin and p53. In our Phase 1 clinical study we use enhancement of expression level of p21 as a biomarker for p53 activation.

Kevetrin demonstrated the potential for a major breakthrough in cancer research by exhibiting an activation of p53. 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.  As a potent anti-proliferative and pro-apoptotic protein, p53 has been shown to play critical roles in the homeostatic health of the human body by activating proteins required to repair DNA and plays a major role in the life cycle of cells by inducing cell cycle arrest and apoptosis to maintain cellular and genetic stability.

The p53 gene is the most commonly disrupted gene in cancer.  In more than 50 percent of all human carcinomas, p53 is limited in its anti-tumor activities by mutations in the protein itself.  Currently, there are greater than 10 million people with tumors that contain inactivated p53, while a similar number have tumors in which the p53 pathway is partially abrogated by inactivation of other signaling components.

p53 sits at the hub of networks that play an essential role in preventing cancer by inducing apoptosis, cell cycle arrest or DNA repair. This protein is regulated by MDM2, which binds to p53 and targets it for degradation. Kevetrin inhibits the MDM2 by phosphorylation and stabilizes the wild type p53 and protects the p53 from degradation. The ability of p53 to regulate transcription of a large number of genes lies at the center of its function as a tumor suppressor.

Kevetrin also degrades the mutant oncogenic p53.  Mutant p53 are the driver of cell proliferation. Turning off these overexpressed genes in human cancer cells preferentially drives them to undergo apoptosis. Kevetrin downregulates c-Myc, HDAC-2 which is over expressed in many cancers.

Kevetrin has broad anticancer effects and potential utility in a wide variety of clinical context for cancer treatment.  Because of the abundance of cancers with p53 disruption, a multi-billion dollar opportunity is present for a new drug that addresses p53 damage to restore it to its normal role as a master regulator of the cell cycle.

We hope Kevetrin will be that drug and data to date lends compelling evidence to our thesis.  We view Kevetrin and its p53 mechanism as a possible major breakthrough in cancer treatment.  Lab and clinical studies have established a solid safety profile for Kevetrin.  We have previously reported that Kevetrin produced encouraging responses with manageable side effects in the current Phase 1 trial and presented this data at the latest American Society of Clinical Oncology meeting.  This poster is available on our website.

The work has been enormous. Now it’s time for us to begin publishing in peer-reviewed journals to complement the peer-reviewed data presented at oncology conferences.  We are now preparing a paper on Kevetrin and p53 for submission to relevant scientific and medical journals. This should attract more attention towards Cellceutix and benefit our shareholders.

Kevetrin is thoroughly protected by its patent, which covers tens of thousands of possible future chemical combinations for new drugs; a potentially very valuable proposition for multiple drug development in the future.

We will be concluding our Phase 1 trial of Kevetrin for solid tumors at the completion of the current cohort.  The final cohort requires six patients. Three of the six patients in the cohort have already completed the required treatments of Kevetrin.  We have been advised that the remaining three patients are currently being recruited.

In July, Cellceutix received an Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for Kevetrin for the treatment of ovarian cancer.  Ovarian cancer is a platinum treated disease where resistance develops quickly.  The Phase 1 trial has provided ample data on the safety of Kevetrin and compelling data with respect to ovarian cancer, some of which has already been publicly disclosed.  The conclusion of the trial fits with our strategic plan to initiate a Phase 2 trial of Kevetrin for ovarian cancer, a notoriously difficult disease to treat and a great area of unmet medical need in a major cancer market.  The protocol for the Phase 2 trial is currently being written, with plans for the trial to be a multi-arm study evaluating Kevetrin as a monotherapy and as a combination therapy.

The pharmacokinetic profile shows that Kevetrin exits the body very quickly, a quality that we believe will be very valuable in Phase 2 clinical trials. So, for Phase 2 trials we will engage the FDA for patient treatments of Kevetrin multiple times per week.

We are encouraged and excited about the clinical direction of Kevetrin, as we believe ovarian cancer represents one of the fastest paths to potential approval as an area of great unmet medical need.  With the conclusion of the Phase 1 trial, clinical development of Kevetrin is going to greatly expand and accelerate as we aim to realize the full potential of this p53-targeting compound.

We are eagerly waiting for a start date from The University of Bologna in Italy on its plan for testing Kevetrin against Acute Myelogenous Leukemia (AML).  The University of Bologna engaged Cellceutix for this trial based upon their review of data on Kevetrin and will be paying for just about all the costs of the trial. The study proposed is a Phase 2 trial evaluating Kevetrin as a single agent and in combination with cytarabine in patients with AML. Over 100 patients are expected to be enrolled in the trial. The protocol was submitted in May 2015 by the principal investigator to the institutional committee. There have been delays in communication due to the summer schedules in Italy. We are awaiting comments on the protocol and only then can have a clearer picture of the timing of the study. 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.

The data from the Phase 1 trial, in conjunction with lab studies, will be used for additional clinical studies of Kevetrin.  In regards to pediatric retinoblastoma, we have already started engagement with the FDA.  We intend to re-engage Beth Israel Deaconess with respect to advancing Kevetrin into Phase 2 studies of renal cell carcinomas.  In a lab study, the hospital combined Kevetrin with sunitinib on cell line 786, a drug-resistant renal cancer, advising us that,  “the Kevetrin/sunitinib combination is the first we’ve used in which actual tumor shrinkage is noted.”  We certainly haven’t forgotten about this commentary and have simply been waiting to collect data from the Phase 1 trial before moving forward.

Kevetrin is only one part of our strategy to grow shareholder value; Brilacidin and our other defensin-mimetics and Prurisol are part and parcel to our plan as well.

Because Brilacidin and the defensin mimetics have both antimicrobial and anti-inflammatory activity, we have developed two strategic pathways, based on the “gateway concept”.  That is, once approved for a gateway indication, we believe we can accelerate the development for subsequent indications.

First, acute bacterial skin and skin structure infections, or ABSSSI, is the gateway for antibiotic opportunities, particularly infections caused by Staphylococcus aureus, including MRSA (Methicillin-resistant Staphylococcus aureus).

Second, oral mucositis is the gateway for anti-inflammatory opportunities, particularly chronic diseases of the skin or mucous membranes.

Novel classes of antibiotics are urgently needed.  Only two new classes of antibiotics have been introduced into the market for ABSSSI over the past 15 years, the oxazolidinones (e.g., linezolid) and the cyclic lipopeptides (e.g., daptomycin). These are active against Gram-positive bacteria, such as MRSA, and are listed on the guidelines for the treatment of complicated skin infections, also known as ABSSSI.  Unfortunately, resistance has been reported to these antibiotics. Moreover, they have multi-day dosing regimens that can lead to non-compliance, which, in turn, can further promote the emergence and spread of resistance.

Other antibiotics have been approved for ABSSSI, but they are analogues of existing classes. This means that bacteria that have already been exposed to a marketed class of antibiotics may exhibit cross-resistance to newer antibiotics from the same class. In fact, over the past year or so, the FDA has approved three new ABSSSI compounds from existing classes of antibiotics:  dalbavancin (lipoglycopeptide); tedizolid (oxazolidinone); and oritavancin (lipoglycopeptide).  Two of these have very long half-lives.   This raises the concern that bacteria have prolonged exposure to subtherapeutic levels, a risk factor for the development of resistance. In addition, it is difficult to discontinue a long half-life drug should adverse events occur. 

Brilacdin and the defensin-mimetics

Brilacidin is the first member of a new class of antimicrobials, the defensin-mimetics, to enter clinical trials.                         

Brilacidin is potently active against S aureus strains including MRSA; this is one of the important pathogens on both the CDC and FDA priority list.  In fact, Brilacidin was granted QIDP (Qualified Infectious Disease Product) designation under the GAIN Act on November 20, 2014.                         

Brilacidin could reduce the overall burden of antibiotic resistance in several ways                                           

Brilacidin rapidly kills bacteria, and has a unique mechanism that makes resistance unlikely to develop                                           

Brilacidin has an intermediate half-life in plasma of ~15 hours after an intravenous dose of 0.6 mg/kg, enabling single-dose treatment of ABSSSI without prolonged exposure at subtherapeutic levels, which is a risk factor for resistance.   As mentioned, newer ABSSSI antibiotics have very long half-lives, and therefore, a higher probability of promoting resistance.                                           

Using single-dose Brilacidin removes non-compliance as a driver of resistance.                                           

Brilacidin has activity on bacteria in a “stationary phase”.  This means it can kill persistent bacteria before they become resistant bacteria. In fact, resistance has not been demonstrated in typical serial passage assays with S aureus, MRSA, and/or S. pyogenes through 20 passages in the presence of sub-lethal concentrations of Brilacidin.                         

Brilacidin Clinical Trials and the Antibiotic Gateway

Brilacidin has been dosed in over 400 subjects in three Phase 1 studies and two Phase 2 ABSSSI studies.

In the Phase 2b study, all tested Brilacidin regimens, including a single 0.6mg/kg dose, showed efficacy similar to a 7-day regimen of daptomycin in adults with ABSSSI.  This included infections caused by MRSA.

Brilacidin was well tolerated.  Except for mild, transient events of numbness and tingling (hypoesthesia/paraesthesia), adverse event rates were similar for the Brilacidin and daptomycin groups.                         

Because elevated blood pressure was observed in previous studies at much higher doses, we carefully monitored patients for blood pressure elevation in this trial. As predicted, with a low single dose of 0.6 mg/kg, there was no observed increase in the rate or severity of blood pressure events, compared to daptomycin, which is not known to affect blood pressure.                         

Comprehensive PK/PD modeling in 2012, after the Phase 2a study, and again in 2015, after the Phase 2b study, showed an exposure-response for both safety and efficacy, and confirmed that a single-dose, rather than higher doses and/or multiple doses, minimizes adverse effects while maintaining high efficacy.                         

Brilacidin data have been presented in multiple peer-reviewed scientific publications and at high-level academic meetings.

The ABSSI data, including the results of the two Phase 2 studies and the results of PK/PD modeling were presented at ICAAC in 2012, ECCMID 2013, ECCMID 2015, and next week at ICAAC 2015.

We met with FDA in July to discuss our data and our proposed Phase 3 program.  The Phase 3 program will include two adequate and well-controlled studies, which is recommended by FDA when ABSSSI is the initial (or only) indication.   In addition, because Brilacidin is a novel antibiotic, we plan to conduct an interim analysis on safety and efficacy in the first group of enrolled subjects in Phase 3.

In addition, this opens the “antibiotic gateway” for defensin-mimetics.  That is, with a first approval in ABSSSI of a novel antibiotic such as Brilacidin, we hope to expand into other areas of infectious diseases of high unmet medical need, such as MRSA infections of prosthetic joints.  This would utilize Brilacidin’s ability to kill bacteria, reduce inflammation and disrupt biofilms.

Gram-negative and anti-fungal program

The defensin-mimetics could address several of the Antibiotic Resistance Threats identified by the Centers for Disease Control and Prevention (CDC, 2013). The medicinal chemistry platform allows us to tailor each new defensin-mimetic to specific types of infections. The Cellceutix pipeline includes pre-clinical stage compounds active against drug-resistant Gram-negative bacteria and azole-resistant Candida. Of interest is the progress made on the treatment of Carbapenem Resistant Enterobacteriaciae or CRE, which is considered an “urgent threat” to public health by the CDC.

Oral Mucositis Clinical Trials and the Anti-Inflammatory Gateway.

Of note, Brilacidin rinse is in a Phase 2 for the prevention and/or treatment of oral mucositis in patients undergoing chemoradiation for head and neck cancer.  As mentioned, Brilacidin has potent anti-inflammatory activity, and its ability to prevent and/or treat oral mucositis has been demonstrated in both an acute and a fractionated radiation model in hamsters. Given the prior work done on Brilacidin to support the ABSSSI program, along with additional animal studies, Cellceutix was allowed to forego Phase 1 and enter Phase 2 in this indication.

The Phase 2 study is recruiting patients at multiple sites. We are looking forward to finishing the study and reviewing the data—this represents the proof of concept for the use of defensin-mimetics as anti-inflammatory agents, and therefore opens a gateway for anti-inflammatory products.

In fact, additional clinical studies are planned for the treatment of chronic inflammatory disorders of the skin and mucous membranes, such as hidradenitis suppurativa and ulcerative proctitis.  We find these to be important areas of unmet medical need, and they highlight the vast potential for these products.

As earlier mentioned, there are four clinical programs underway.  Briacidin IV is poised to enter Phase 3 for the treatment of ABSSSI, opening the gateway for antibiotic indications. Brilacidin oral rinse is in Phase 2 for the prevention of oral mucositis, opening the gateway for anti-inflammatory indications. Kevetrin is in phase 1 for the treatment of late-stage solid tumors, with promising early data on the p53 pathway, along with an orphan designation for ovarian cancer.

Lastly in the clinic, Cellceutix is conducting a Phase 2 study of Prurisol as a new oral treatment for plaque psoriasis.  Prurisol is a small molecule that acts through immune modulation and PRINS reduction. Prurisol has been found to be effective against psoriasis in animal models, both in induced psoriasis as well as a xenograft model with human psoriatic tissue.  Images of lab studies showing the dramatic effect of Prurisol compared to controls are available on our website.  The Phase 2 study is currently enrolling at multiple sites. Prurisol is eligible for 505(b)(2) regulatory pathway because it is an active moiety of an already approved compound (abacavir).

Cellceutix also wishes to inform shareholders that a proxy statement will be filed with the Securities and Exchange Commission for the Company’s first Annual General Meeting of Shareholders.  It will give us an opportunity to meet shareholders and select auditors and discuss corporate matters. More details are to follow.

As you can see, this is an exciting and productive time for the Company.  We look forward to sharing information about these studies in future updates.