Study results, through the first two cohorts of patients treated, support Brilacidin as a novel and promising anti-inflammatory drug candidate
BEVERLY, MA – March 21, 2017 (GLOBE NEWSWIRE) Cellceutix Corporation, (OTCQB:CTIX) (“the Company”), a clinical stage biopharmaceutical company developing innovative therapies with dermatology, oncology, anti-inflammatory, and antibiotic applications, is pleased to inform shareholders that the Company today announces additional favorable topline findings as part of interim analysis from its ongoing Phase 2a Proof-of-Concept (PoC) study of Brilacidin for the treatment of Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS), two types of Inflammatory Bowel Disease (IBD).
As discussed in a prior press release, a large unmet need exists in the marketplace for treating IBD patients with newer, non-biologic therapies, which the Company believes Brilacidin, with its unique mechanism of action, is showing the potential of becoming.
Presented below is information on Cellceutix’s study of Brilacidin in UP/UPS, including detailed trial results observed through the first two cohorts (12 patients). Three of six patients in the third and final cohort have been enrolled this week and the Company anticipates the full study will be completed in 2Q2017.
CTIX-BRI-206 is a Phase 2a open-label, dose-escalation study, evaluating the efficacy, safety and pharmacokinetics (PK) of 3 dosing regimens of Brilacidin—50 mg (Cohort A), 100 mg (Cohort B) and 200 mg (Cohort C)—in patients with active mild-to-moderate UP/UPS. Brilacidin is given daily as a retention enema across 42 consecutive days (6 weeks) of treatment. Endoscopic evaluation (photos and videos) of rectum and mucosa up to 40 cm from the anal verge in patients is performed at Screening and at End of Treatment (Day 42).
The Primary Efficacy Endpoint of the Brilacidin UP/UPS trial uses Modified Mayo Disease Activity Index (MMDAI) scoring, a common measurement tool in managing Ulcerative Colitis preferred by many IBD specialists, to determine Clinical Remission at Day 42, as defined by meeting all three contributing criteria:
- Stool Frequency (SF)—an improvement or no change from baseline
- Rectal Bleeding (RB)—subscore = 0 (no blood seen)
- Endoscopy Findings (EF)—subscore ≤ 1 (mild disease; normal or inactive disease)
Secondary Efficacy Endpoints include: change in MMDAI score, Full and Partial (defined below); and change in patient Quality of Life (as assessed by the Short Inflammatory Bowel Disease Questionnaire or SIBDQ):
- Full MMDAI = SF + RB + PGA (Physician Global Assessment) + EF subscores
- Partial MMDAI = SF + RB + PGA subscores
After 6 weeks (42 days) of daily treatment with Brilacidin all 12 patients from the first two cohorts experienced a beneficial response as measured by MMDAI scoring parameters.
Primary Efficacy Endpoint of Clinical Remission (accounting for Stool Frequency, Rectal Bleeding and Endoscopy Findings subscores)—50 percent of patients in Cohort A (3 of 6) and 50 percent of patients in Cohort B (3 of 6) met this endpoint; all 6 of the remaining patients in Cohorts A and B met 2 of the 3 criteria (Partial Response).
Full MMDAI (accounting for Stool Frequency, Rectal Bleeding, Physician’s Global Assessment and Endoscopy Findings subscores)—notable improvements observed in 10 of 11 patients (one patient declined endoscopy at end of treatment):
· 100 percent reduction in 2 patients in Cohort A and 2 patients in Cohort B
· 50-75 percent reduction in 2 patients in Cohort A and 4 patients in Cohort B
· 20 percent reduction in 1 patient in Cohort A
Partial MMDAI (accounting for Stool Frequency, Rectal Bleeding and Physician’s Global Assessment subscores)—notable improvements observed in 11 of 12 patients:
· 100 percent reduction in 3 patients in Cohort A and 3 patients in Cohort B
· 50-83 percent reduction in 2 patients in Cohort A and 3 patients in Cohort B
· 0 percent reduction in 1 patient in Cohort A
Patient Quality of Life (as assessed by the Short Inflammatory Bowel Disease Questionnaire, SIBDQ)—notable improvements in all 12 patients; 50 percent of patients in Cohort A (3 of 6) and 80 percent of patients in Cohort B (5 of 6) reported significant improvements of 15 points to more than 50 points higher on the 70-point SIBDQ scale.
Other Clinically Meaningful Observations
· Endoscopy subscore of ≤ 1 met in 7 of 11 patients (1 patient declined final endoscopy).
· PGA subscore improved for 10 of 12 patients.
· Rectal Bleeding subscore improved for all 12 patients.
· Stool Frequency subscore demonstrated improvement by study end for all patients who were abnormal at study start.
· Brilacidin was generally well-tolerated with No Serious Adverse Events (SAEs).
· All 16 Adverse Events (AEs) experienced by a total of 6 patients were rated by Investigators as “Unlikely Related” or “Not Related” to treatment.
· Clinical Laboratory Review (CLR): No clinically significant trends, changes or abnormalities observed in blood chemistry, hematology and urinalysis.
· Vital Signs: No clinically significant changes seen.
· Limited systemic exposure to Brilacidin as measured by plasma concentrations:
o Cohort A (50 mg): All patients had concentrations <100 ng/mL
o Cohort B (100 mg): Average maximum concentration was 215 ng/mL
· In comparison, maximum drug concentrations in plasma previously seen in CTIX-BRI-204, a successfully completed Phase 2b Trial of Brilacidin by intravenous (IV) dosing at 0.6 mg/kg and 0.8 mg/kg for Acute Bacterial Skin and Skin Structure Infection (ABSSSI), were approximately 9,000 ng/mL and 12,000 ng/mL respectively.
“Of particular note in the results observed so far in the Brilacidin UP/UPS trial are clear signs of mucosal healing in patients as determined by independent review of endoscopic images and videos by practicing gastroenterologists,” said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Cellceutix. “A changing IBD treatment paradigm, as well as a regulatory one, is placing an increased emphasis on establishing Clinical Remission based on objective criteria, such as validated endoscopic response, and not just relying on subjective scoring systems. That a majority of patients treated with Brilacidin at the end of 6 weeks showed mild disease or no disease at all based on MMDAI Endoscopy subscores reinforces Brilacidin’s therapeutic potential in treating IBD.”
“To see such consistently strong results through the first two cohorts of UP/UPS patients treated with Brilacidin is highly promising,” commented Leo Ehrlich, Chief Executive Officer at Cellceutix. “With planned newer formulations, foam and oral, we believe Brilacidin could one day be extended into treating a number of chronic IBD indications. The Company looks forward to continuing to share results with investors and the public across the coming months and will be presenting topline findings at the 2017 Drug Discovery and Therapy World Congress to be held July 10-13, 2017 in Boston.”
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Brilacidin is Cellceutix’s lead drug candidate in its defensin mimetic franchise. Modeled after Host Defense Proteins (HDPs), the “front-line” of defense in the immune system, it is a small, non-peptidic, synthetic molecule that kills pathogens swiftly and thoroughly. Just as importantly, Brilacidin also functions in a robust immunomodulatory capacity, lessening inflammation and promoting healing. Due to its unique properties, Cellceutix is studying Brilacidin’s effect on oral mucositis (under Fast Track designation) and on ulcerative proctitis/proctosigmoiditis (UP/UPS) in Phase 2 trials. Additional trials of Brilacidin are planned in other conditions, including: hidradenitis suppurativa and acne. Brilacidin is also being developed under FDA’s Qualified Infectious Disease Product (QIDP) designation as an antibacterial product for Acute Bacterial Skin and Skin Structure Infections (ABSSSI)—qualifying it for Fast Track and possible Priority FDA Review and a potential extra 5 years of United States market exclusivity upon drug approval.
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About Inflammatory Bowel Disease
Inflammatory Bowel Disease (IBD), with Ulcerative Colitis (UC) and Crohn’s Disease (CD) the most common forms, are lifelong, chronic conditions characterized by inflammation of the gastrointestinal (GI) track with symptoms fluctuating between periods of exacerbation and remission. The peak age for UC onset is between 30 and 40 years and between 20 and 30 years for CD. Approximately 20 percent of patients with UC experience active “moderate” or “severe” disease and 50 percent are in remission. Seventy percent of those with active disease of any severity and 30 percent of those in remission will experience episodes in the following year. In CD, 55 percent of patients in remission will have a relapse across the next year, with 11 percent having chronically active disease. Approximately 1.7 million people in the U.S. have IBD, with the total number of cases increasing by 70,000 cases annually. IBD greatly affects a person’s quality of life, including increased emotional distress and a reduced ability to work. Total societal costs, in the U.S. alone, attributable to IBD are estimated to range between $14.6 and $31.6 billion. The considerable economic burden of IBD makes an accurate diagnosis, coupled with effective treatment at the onset of symptoms, a critical component of IBD care.
Ulcerative proctitis (UP), a limited type of ulcerative colitis (UC), is a mucosal inflammatory disease of unknown cause involving only the rectum. When it involves both the rectum and the distal colon, it is called Ulcerative Proctosigmoiditis (UPS). It is characterized by inflammation, redness, and ulcerations of the mucosa. The course of the disease is variable and ranges from complete resolution to easily maintained remission to chronic relapses or refractory disease. Diagnosis can occur at any point in life, with approximately 30-50 percent of patients developing more extensive UC. There is currently no cure. According to estimates provided by GlobalData, the worldwide UC market, which includes products for UP/UPS, is expected to increase at a compound annual growth rate of 4.7 percent, from $4.2 billion in 2012 to approximately $6.6 billion by 2022.
About Cellceutix’s Proof-of-Concept (PoC) UP/UPS Trial Design
This trial is being conducted in an overseas hospital/clinic setting with Brilacidin being administered with water in an enema. A foam formulation of Brilacidin for use in future studies is planned and would be expected to improve patient convenience and study results. The primary objective of Cellceutix’s Proof-of-Concept (PoC) trial is to assess the frequency of clinical remission (defined using Modified Mayo Disease Activity Index [MMDAI] scoring) with Brilacidin administered per rectum by enema in patients with active UP or UPS after 6 weeks of treatment. Secondary objectives include: evaluation of safety and tolerability of Brilacidin when administered per rectum; assessment of systemic exposure and/or pharmacokinetics of Brilacidin when administered per rectum; assessment of the efficacy of Brilacidin by change in MMDAI at Day 42/Week 6 and Partial MMDAI during treatment and by biomarker evaluation (from serum, feces, and rectum/sigmoid biopsy samples); evaluation of change in patient-reported quality of life (by the Short Inflammatory Bowel Disease Questionnaire); and estimation of statistical power for subsequent trial(s) in UP and UPS. The PoC trial includes 18 patients divided evenly into three cohorts. Cohort A receives 50 milligrams (mg) of Brilacidin once daily administered per rectum as a retention enema for 42 days. Dosing is increased to 100 mg and 200 mg once daily for 42 days for Cohort B and Cohort C, respectively. Endoscopic evaluation of the rectum and mucosa up to 40 cm from the anal verge is performed at screening and at the end of treatment/Day 42 (± 3 days). Per protocol, a Safety Committee reviews safety and retention data (clinical laboratory findings, vital signs, adverse events, retention times) after 21 days of therapy for all six patients in each cohort before proceeding with initiating enrollment into the subsequent cohort.