Cellceutix reported in August 2014 that it had stabilised the formulation of brilacidin, eliminating the need for refrigeration and allowing storage at room temperature. This breakthrough positions the company to proceed with development for the treatment of diabetic foot ulcers, followed by ophthalmic and otic formulations  .
Innovation Pharmaceuticals is developing a foam formulation of brilacidin  .
In May 2020, Innovation Pharmaceuticals released preclinical data for brilacidin from antiviral assays in COVID-2019 infections   .
In May 2020, Innovation Pharmaceuticals announced that Lab testing conducted at a US based Regional Biocontainment Laboratory (RBL) supported Brilacidin’s antiviral activity in directly inhibiting SARS-CoV-2 in cellular assays, with a molecular screening study of 11,552 compounds also supporting it as a promising novel coronavirus treatment. Additional pre-clinical and clinical data support Brilacidin’s potential to inhibit the production of IL-6, IL-1b, TNF-a and other pro-inflammatory cytokines and chemokines, which have been identified as central drivers in the worsening prognoses of COVID-19 patients  . As of March 2020, Brilacidin’s potential inhibitory activity as a small molecule drug against COVID-2019 infections was being evaluated at one of 12 Regional Biocontainment Labs (RBL) in the US. company released the data from the research, demonstrating direct inhibition of SARS-CoV-2. In April 2020, Innovation Pharmaceuticals announced the brilacidin as a promising and unique (a 3 in 1 combinatio'n; antiviral, immune/anti-inflammatory, and antimicrobial) anti-COVID-19 therapeutic candidate     .
Inflammatory bowel disease
In February 2020, Innovation Pharmaceuticals completed the phase I trial and announced that the trial met its primary endpoints. The randomised trial, initiated in January 2020 and was designed to assess the safety, tolerability and pharmacokinetics of oral formulation of brilacidin in healthy volunteers (NCT04240223; BC250; EudraCT2019-003367-22). The single-center enrolled 9 healthy volunteers in the UK   .
In January 2019, Innovation Pharmaceuticals released favourable pharmacokinetic data from a simulated gastric fluid model, testing the stability of an oral formulation of brilacidin, for the treatment of inflammatory bowel disease  .
Skin and soft tissue infections
Following a positive end-of-phase II meeting with the US FDA in July 2015, Innovation Pharmaceuticals plans to advance brilacidin to phase III development in patients with ABSSSIs. The trial is expected to begin in 2017. The trial initiation is dependent on reaching SPA agreement with the FDA   . As required by the FDA, the programme will consist of two phase III studies, the first of which will include an interim analysis for early assessment of efficacy and safety. In September 2015, Cellceutix submitted a Paediatric Study Plan to the US FDA with the aim of expanding the use of brilacidin to children. Lab testing of brilacidin which is to be used in the upcoming phase III trials was completed in December 2015. In February 2016, the company announced that it has submitted a Special Protocol Assessment (SPA) request, including information requested by the US FDA to initiate the planned phase III clinical trials of Brilacidin, for the treatment of ABSSSI caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). The SPA request includes details of intravenous vancomycin with an option to switch to oral linezolid after three days of therapy as a choice of comparator for the phase III programme       .
In August 2014, Cellceutix completed a randomised, double-blind phase IIb trial designed to assess the safety and efficacy of three dosing regimens of brilacidin, compared with daptomycin, in patients with ABSSSIs caused by Staphylococcus aureus (including MRSA) and Streptococcus pyogenes (NCT02052388). The trial was initiated in February 2014 and enrolled 215 patients in the US. The trial demonstrated that a single intravenous dose of brilacidin delivered comparable outcomes to a seven-day dosing regimen of the FDA-approved drug, daptomycin, in patients with ABSSSIs. In October 2014, the company reported top-line data from the trial and additional data from the microbiological intent-to-treat population was released in December 2014. In April 2015, the company reported that it has gathered microbiological data from bacterial pathogens isolated in the trial along with pharmacokinetic and pharmacodynamics data and also in-depth evaluated the safety profile of brilacidin against that of daptomycin in this patient population. The data will determine the appropriate dose of brilacidin for a planned phase III registration-enabling trial                  .
In September 2015, Cellceutix had developed a population pharmacokinetic model for brilacidin using data from three phase I and two phase II trials in patients with ABSSSI. The model was developed to describe the time-course of brilacidin in plasma and to identify predictor's of pharmacokinetics  .
Brilacidin was associated with high and sustained clinical response rates across all dose groups in a phase IIa trial in patients with ABSSSIs caused by either meticillin-susceptible (MSSA) or meticillin-resistant (MRSA) Staphylococcus aureus (PMX63-203; NCT01211470). Patients were randomised to one of three dosing regimens of brilacidin or daptomycin, and were assessed at 48 and 72 hours for clinical and microbiologic response. Brilacidin was administered once-daily for five days followed by two days of placebo. Daptomycin was administered once-daily for seven days. Patients were re-evaluated at day 10 to 15 for test of cure, and again for safety at four weeks. In September 2011, PolyMedix received clearance from European regulatory agencies to conduct the trial in Europe. Enrolment of 215 patients in Canada, Ukraine, Russia and other European sites was completed in January 2012      .
PolyMedix completed a phase I trial (PMX63-103) of brilacidin in healthy volunteers in the US in February 2011. The randomised, double-blind study evaluated the tolerability and pharmacokinetics of intravenous brilacidin, given with an initial loading dose followed by once-daily dosing at its highest anticipated therapeutic dose for up to 14 days, in 16 subjects    . Volunteers in this study reported experiencing temporary paraesthesia of the face and fingers during brilacidin, similar to those seen in previous phase I studies. To determine the mechanism of the effect, PolyMedix conducted additional in vitro and in vivo studies, and based on these data, PolyMedix believes that the paraesthesia may be associated with temporary interactions with specific potassium, sodium or acid sensing ion channels located on sensory nerve fibres   . After completion of the phase I trial, PolyMedix intended to hold discussions with the FDA concerning further development of the drug in the US  .
In March 2010, PolyMedix released final results for its phase Ib trial of brilacidin that assessed the safety of repeated dosing  . The study was designed to mimic the expected clinical dosing regimen. Healthy volunteers received brilacidin or placebo twice a day for five days at doses ranging from 0.1-0.6 mg/kg every 12h, 24h or 48h, for a total of 5 to 10 doses. Results showed that the optimal dose for phase II investigation was found to be 0.3 mg/kg/day (0.3 mg/kg every 12 hours or 0.6 mg/kg every 24 hours)       .
In May 2008, PolyMedix received a notice of no objection from Health Canada to begin phase I trials for brilacidin. The first phase I trial was subsequently initiated in August 2008 and assessed the safety of brilacidin in a dose-escalation study in approximately 30-50 healthy volunteers who received a single IV dose of brilacidin  . The subjects were grouped into different cohorts with different dosage levels which allowed for the study of the effects of increased dosages. Positive results from this phase Ia trial were presented in December 2008   .
In December 2014, the US FDA granted the qualified infectious disease product (QIDP) designation to brilacidin for the treatment of ABSSSI  . Innovation Pharmaceuticals also intends to file for fast track designation in this indication, in the US. The company believes it may be possible to market brilacidin before the planned phase III trial has been completed. Brilacidin is eligible for additional FDA incentives in the approval and marketing path, including Fast Track designation and Priority Review for development and a potential five-year extension of market exclusivity under the Generating Antibiotics Incentives Now (GAIN) Act    .
Stomatitis (oral mucositis)
In November 2019, the US FDA waived initial Pediatric Study Plan requirement for brilacidin, for the prevention of severe oral mucositis in head and neck cancer patients receiving chemoradiation, in pediatric populations. Innovation Pharmaceuticals will focus on development of brilacidin in for the treatment of oral mucositis in adult patients  .
In December 2018, Innovation Pharmaceuticals announced that the US FDA completed an End-of-Phase 2 meeting concerning the continuing development of Brilacidin oral rinse to decrease the incidence of severe oral mucositis (SOM) in head and neck cancer (HNC) patients receiving chemoradiation. In October 2018, the company had reported that the US FDA had granted an End-of-Phase 2 meeting for its clinical development programme of brilacidin oral rinse   .
In March 2019, Innovation Pharmaceuticals reported that the documentation for the European Medicines Agency (EMA) March 15, 2019 submission cycle requesting scientific advice to advance brilacidin oral rinse in a phase III programme for the prevention of severe oral mucositis in head and neck cancer patients receiving chemoradiation has been completed. EMA granted a meeting with Innovation Pharmaceutical's subsidiary, IPIX Pharma, in April 2019   .
In November 2015, Cellceutix reported that the US FDA had granted Fast Track Designation to the oral rinse formulation of brilacidin for the treatment of oral mucositis. Additionally, in October 2017, Innovation Pharmaceuticals reported that it intends to apply for FDA Breakthrough Therapy Designation, and follow a similar expedited path in Europe, subject to condition that the CTIX-BRI205 phase II trial of brilacidin [see below] yields comparable safety and efficacy results, to those observed at interim    .
A phase II trial of brilacidin met its primary and secondary endpoints, including reduced incidence of severe stomatitis experienced by patients during radiation therapy, in December 2017, and subsequently the trial was completed (CTIX-BRI205; NCT02324335). The trial evaluated the efficacy and tolerability of brilacidin (45 mg/15 ml oral rinse), as compared with a placebo rinse, for the prevention of stomatitis in patients with head and neck cancer undergoing chemoradiation. The primary endpoint was assessed by sequential WHO oral mucositis score at multiple time-points. Innovation had completed the trial in November 2017. Positive preliminary interim efficacy, pharmacokinetics and adverse events data from the trial were released by Cellceutix, in March 2017. Updated results from the trial were reported in January 2018, April 2018 and May 2018. The trial met its primary and secondary endpoints   . The randomised 1:1, parallel, double-blind trial was initiated in August 2014 and enrolled 61 patients in the US             .
In October 2014, the IND for a phase II trial of brilacidin (brilacidin-OM) for the treatment of oral mucositis became effective, and selected a trial site in the US  . Cellceutix submitted IND application with the US FDA in September 2014  . The company received the final IND-enabling toxicology report for brilacidin in this indication in August 2014  . In December 2014, Cellceutix received approval from the Institutional Review Board for initiation of the study for prevention of oral mucositis in patients undergoing chemoradiation for treatment of head and neck cancer     .
In preclinical trials, brilacidin demonstrated immunomodulatory, antibacterial, anti-biofilm and anti-inflammatory properties, which support the phase II trial of brilacidin for prevention of oral mucositis   .
Brilacidin-OM reduced the occurrence of severe ulcerative oral mucositis by more than 94% as compared with placebo in an animal model  . Brilacidin demonstrated the ability to significantly reduce ulcerations in an animal model of radiation-induced stomatitis. The agent was administered as a preventive oral rinse thrice daily for 20 days. No adverse events were reported  . Brilacidin has also shown positive results in a 28-day acute radiation model, and a 35-day fractionated radiation model  . PolyMedix was working toward filing an IND with the US FDA to initiate a clinical trial in early 2013 in patients with stomatitis. Following its acquisition of PolyMedix, Cellceutix announced that it will prioritise completion of the IND filing to pursue development in the oral mucositis indication   .
Cellceutix has filed an application with the US FDA in December 2013 requesting orphan drug status for brilacidin in this indication  .
In January 2020, Innovation Pharmaceuticals initiated a phase I trial to assess the safety, tolerability, and pharmacokinetics of delayed release tablets of brilacidin in healthy volunteers. The randomised, double-blind, placebo-controlled trial intends to enrol approximately nine patients in the UK. In the same month, the company completed dosing in the trial. After reviewing the safety findings from the first cohort, the Dose Escalation Committee (DCE) recommended to progress dosing to the second cohort. In December 2019, the United Kingdom’s Medicines and Healthcare products Regulatory Agency granted approval to Innovation Pharmaceuticals to conduct a phase I trial for delayed release tablets of brilacidin in healthy volunteers, for the development in ulcerative colitis       .
In June 2017, Cellceutix completed a phase IIb proof-of-concept trial evaluating efficacy, pharmacokinetics, safety and tolerability of brilacidin, as a retention enema at 50 mg, 100 mg, and 200 mg once daily for six weeks, in patients with ulcerative colitis (ulcerative proctitis/ulcerative proctosigmoiditis) (CTIX-BRI-206)  . The open label, dose escalation, trial initiated in June 2016 enrolled 17 patients, in Europe. The primary endpoint was to assess the frequency of clinical remission with brilacidin administered per rectum by enema, in patients with active ulcerative proctitis after 6 weeks of treatment. In July 2016, the first patient was enrolled. In October 2016 and November 2016, the company reported pharmacokinetics and efficacy data of patients treated in the first cohort of 50 mg brilacidin, demonstrating a well-tolerated drug safety profile, devoid of measurable systemic absorption. In December 2016, the company initiated the second cohort of brilacidin 100mg once daily, which was administered as a retention enema. In January 2017, enrolment in the second cohort was completed and brilicidin was well tolerated. In February 2017, enrolment was initiated in the third cohort of the trial. Patients received 200mg of brilacidin in this cohort. In January 2017, the company released phase II data showing that brilacidin was well-tolerated with no severe adverse events reported and no detection of measurable systemic absorption. Preliminary review in patients in the first cohort showed meaningful improvements for 5 of the 6 patients, including noticeable reductions in ulceration and bleeding               . In March 2017, the company released additional updated results for the first two cohorts from this study. In May 2017, Cellceutix completed ulcerative proctitis patient enrolment in the third and the last cohort   .
In November 2014, Innovation Pharmaceuticals announced that IND-enabling studies of brilacidin in ulcerative colitis are underways   .
Innovation Pharmaceuticals plans to conduct gastroenterological studies of brilacidin as foam and tablet formulations  .
In September 2019, Innovation Pharmaceuticals announced that non-clinical studies for oral formulation for Brilacidin met the in vitro specifications for selective delivery to the colon  .
Cellceutix reported in September 2013 of its plans to assess the scientific data showing the potential of brilacidin for the treatment of inflammatory bowel diseases  . Since then, the company conducted preclinical studies evaluating immunomodulatory properties of brilacidin in animal models of Crohn's disease, ulcerative colitis and inflammatory bowel disease  .
In March 2020, Innovation Pharmaceuticals announced that the testing of brilacidin as a novel experimental treatment against the latest coronavirus is scheduled to commence in third week of March 2020. Innovation Pharmaceuticals will research its drug candidate, brilacidin with US based Regional Biocontainment Lab (RBL) to evaluate its potential antiviral and anti-inflammatory properties for novel coronavirus treatment. The company has submitted preliminary summary of brilacidin's potential as a novel coronavirus treatment to the Biomedical Advanced Research and Development Authority (BARDA), which is dedicated to rapidly identifying and funding medical countermeasures to the COVID-19 outbreak   . Innovation Pharmaceuticals intends to develop brilacidin, for the treatment of coronavirus infections designated as COVID-2019 infections and potentially Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV)   .
Innovation Pharmaceuticals plans to initiate clinical trials of brilacidin for the treatment of atopic dermatitis, acne and hidradenitis suppurativa     . In January 2018, Innovation Pharmaceuticals reported that the company was in discussion with a leading drug formulator to develop topical formulation/formulations of brilacidin for these three dermatology indications  .
Preclinical studies demonstrated good minimum inhibitory concentration values when brilacidin was tested against Propionibacterium species, expressed in acne, as compared with other antibiotics, such as erythromycin, clindamycin, minocycline, doxycycline and metronidazole  .
Preclinical trials of an ophthalmic formulation have been conducted by Cellceutix for various ophthalmic infections, including keratitis and conjunctivitis. The studies showed promising pharmacokinetic outcomes and antimicrobial activity  . The University of Pittsburgh conducted preclinical safety and tolerability studies and Iris Pharma investigated the pharmacokinetic profile of brilacidin for use in ocular infections. Dr Reddy's Laboratories are involved in the formulation development of brilacidin-ocular.
In December 2015, Innovation Pharmaceuticals plans to start a retinoblastoma program including formulation and toxicity studies, additional ototoxicity studies with brilacidin in different concentrations and proceed with studies in gram- negative and anti-fungal applications for brilacidin. The programme is intended to be initiated by mid-2016  .
In August 2014, Cellceutix reported that it is developing its new room temperature-stable formulation of brilacidin for the treatment of infected diabetic foot ulcers. Innovation Pharmaceuticals intends to conduct clinical trials for infected diabetic wounds  . In May 2014, the company released preclinical data demonstrating wound healing properties of brilacidin in a diabetic rat model. Innovation Pharmaceuticals is planning to conduct additional preclinical trials in infected diabetic wound models  .
Innovation Pharmaceuticals is also conducting preclinical studies of brilacidin for otitis media and otitis externa  . The company will develop its new room temperature-stable formulation for the treatment of otitis media  . Dr Reddy's Laboratories are involved in the formulation development of brilacidin-otic.
PolyMedix suspended the preclinical development of brilacidin as topical (ophthalmic infections) and oral (intestinal infections) applications pending further allocation of resources, according to its Form 10-K (filed 12 March 2010).
In June 2015, Cellceutix reported that it is in the process of completing formulation work for brilacidin in treating hidradenitis suppurativa  . The company had previously planned a pre-IND meeting with the US FDA for a phase II trial for this indication but decided it will only advance this programme after review of preliminary data from the oral mucositis trial.
In October 2018, Innovation Pharmaceuticals secured financing for up to $US10 million, which includes an initial net placement of approximately $US2.2 million over the course of the first 30 days. The company intends to utilise these funds for the continued advancement of brilacidin for oral mucositis, kevetrin [see Adis Insight Drug profile 800028294] for ovarian cancer and prurisol [see Adis Insight Drug profile 800028312] for psoriasis  .
In April 2015, Cellceutix entered into a common stock purchase agreement with Aspire Capital Fund. Aspire agreed to purchase upto $US30 million of the company's common stock over 3 years. The proceeds will be used to support brilacidin development and development of other pipeline candidates. Previously, Aspire Capital had completed two similar transactions with the company totalling $US30 million  .
In March 2013, PolyMedix announced a proposed public offering of common stock, which was expected to raise approximately $US25 million. Potential proceeds were to be used to conduct clinical trials of brilacidin and general corporate uses  .
In November 2010, PolyMedix was awarded two grants totalling $US488 958 under the Qualifying Therapeutic Discovery Project (QTDP) programme, created as part of the Patient Protection and Affordable Care Act of 2010. The maximum grant amount was awarded for two of PolyMedix's programmes, including the development of brilacidin  .
PolyMedix developed brilacidin as a topical rinse for the treatment of stomatitis and received a Phase I grant from the NCI to further explore the potential of this compound in addressing this unmet medical need   .
In March 2010, PolyMedix closed a debt financing for gross proceeds of $US10 million, and in November 2009, the company closed an equity financing for gross proceeds of $US20.7 million. This provided significant additional financing to fund some of the continued clinical development of brilacidin and delparantag.
PolyMedix secured a $US14 million credit facility with Hercules Technology II, L.P. in April 2010. PolyMedix intended to use proceeds from the facility to fund certain phase III enabling activities for brilacidin and delparantag, including manufacturing and toxicology studies  .