Brilacidin - Alfasigma/Innovation Pharmaceuticals
Alternative Names: Brilacidin tetrahydrochloride; Brilacidin-Ocular; Brilacidin-OM; Brilacidin-Otic; Defensin-mimetic - Innovation Pharmaceuticals; HDP-mimic - Innovation Pharmaceuticals; Host defense protein-mimic - Innovation Pharmaceuticals; PMX-30063Latest Information Update: 26 Jun 2023
At a glance
- Originator PolyMedix
- Developer Innovation Pharmaceuticals
- Class Amides; Anti-infectives; Anti-inflammatories; Antiacnes; Antibacterials; Antivirals; Foot disorder therapies; Guanidines; Peptidomimetics; Pyrimidines; Pyrrolidines; Skin disorder therapies; Small molecules
- Mechanism of Action Cell membrane permeability enhancers; Cell membrane structure modulators; Immunomodulators; Type 4 cyclic nucleotide phosphodiesterase inhibitors; Virus internalisation inhibitors
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Orphan Drug Status
No
Orphan designation is assigned by a regulatory body to encourage companies to develop drugs for rare diseases.
- New Molecular Entity Yes
- Available For Licensing Yes - COVID 2019 infections
Highest Development Phases
- Phase II COVID 2019 infections; Skin and soft tissue infections; Stomatitis; Ulcerative proctitis
- Preclinical Alphavirus infections; Bunyavirus infections; Coronavirus infections; Ebola virus infections; Marburg virus disease; Nipah virus infections; West Nile virus infections; Zika virus infection
- No development reported Acne; Atopic dermatitis; Diabetic foot ulcer; Hidradenitis suppurativa; Inflammatory bowel diseases; Otitis; Wounds
- Discontinued Intestinal infections; Ophthalmic infections; Ulcerative colitis
Most Recent Events
- 21 Jun 2023 Innovation Pharmaceuticals has patents pending for Brilacidin in fungal diseases in USA
- 21 Jun 2023 Innovation Pharmaceuticals receives notice of allowance for patent covering arylamide compounds for treatment of viral infections in USA
- 06 Jun 2023 Innovation Pharmaceuticals has patent protection for Brilacidin in the US
Development Overview
Introduction
Brilacidin is a non-peptidic, synthetic, amphiphilic, small molecule, defensin biomimetic, being developed by Innovation Pharmaceuticals (formerly Cellceutix), for the treatment of inflammatory bowel diseases, ulcerative proctitis, ulcerative proctosigmoiditis, atopic dermatitis, viral infections including COVID-2019 infections, bunyavirus infections, alphavirus infections, Ebola virus infection, Marburg virus disease, Nipah virus infection, West Nile virus infection, Zika virus infection, acne, hidradenitis suppurativa, pan-staphylococcal infections, including methicillin-resistant strains (MRSA) and for the prevention of stomatitis (oral mucositis). Brilacidin directly lyses the bacterial cell membrane by penetrating into it resulting in disruption of barrier and membrane-associated metabolic functions and subsequent bacterial death. It also induces misfolding of cytoplasmic protein. The drug lessens inflammation and promotes healing. It is effective against both rapid growth phase and stationary phases of bacteria and has the potential to function as a single-dose therapy against multi-drug resistant bacteria or superbugs. Thus, brilacidin is capable of disrupting biofilms and has the potential to be used for biofilm-related infections caused by Staphylococcus aureus. It is active against both gram-positive and gram-negative bacteria. Brilacidin is not intended for mycobacterial infections. The product is designed to offer advantages such as a low probability for drug resistance, broad-spectrum activity, ability for single-dose intravenous administration and inexpensive to produce. Brilacidin’s antiviral mechanism of action is its ability to attack the coronavirus directly by disrupting viral membrane integrity. Clinical development of intravenous formulation is underway in Canada, Russia, Ukraine and the US for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). Clinical development of brilacidin oral rinse (topical formulation) is underway for the prevention of stomatitis in the US. Clinical development of a retention enema (rectal formulation) of brilacidin is underway in the US. Clinical development of tablet formulation is ongoing for the treatment of inflammatory bowel diseases and ulcerative proctitis in the UK and the US, respectively. Clinical development for COVID-2019 infections is ongoing in the US and Russia. Preclinical development for coronavirus infections, bunyavirus infections and alphavirus-infections, is ongoing in the US. Preclinical development for the treatment of acne, inflammatory bowel disease (oral formulation), atopic dermatitis and hidradenitis suppurativa is underway in the US.
Innovation Pharmaceuticals was also developing Brilacidin as a vaccine for COVID-2019 infections [see Adis Insight Drug profile 800057896].
Preclinical development was underway for the treatment of intestinal infections and ophthalmic infections, but development was discontinued. Preclinical development was ongoing for diabetic foot ulcer, otitis and wounds, however, no recent development has been reported.
Brilacidin is the first defensin mimetic antibiotic compound to enter human clinical trials for systemic use. The compound emerged from a PolyMedix research programme [see AdisInsight drug profile 800020520] that focused on anti-infectives, which is now owned by Innovation Pharmaceuticals. The company is developing an oral formulation of brilacidin for the treatment of extensive forms of inflammatory bowel diseases including Crohn's disease, and a topical formulation of brilacidin for inflammation and immunologic conditions, including atopic dermatitis and acne.
In June 2017, Cellceutix changed its name to Innovation Pharmaceuticals [1] .
Innovation Pharmaceuticals is looking for partnership opportunities for the brilacidin in COVID-19 infections [2] .
As at August 2022, no recent reports of development had been identified for preclinical development in Acne in USA (Topical), preclinical development in Atopic-dermatitis in USA (Topical), preclinical development in Hidradenitis suppurativa in USA (Topical).
As at February 2023, no recent reports of development had been identified for phase-I development in Ulcerative-proctitis (In volunteers) in USA (PO, Controlled release), preclinical development in Inflammatory-bowel-diseases in USA (PO, Controlled release).
As at March 2023, no recent reports of development had been identified for phase-I development in Inflammatory-bowel-diseases (In volunteers) in United Kingdom (PO, Controlled release).
Company Agreements
In July 2019, Innovation Pharmaceuticals entered into a license agreement with Alfasigma to develop and commercialise locally-administered brilacidin globally, for the treatment of ulcerative proctitis/ulcerative proctosigmoiditis (UP/UPS). Innovation Pharmaceuticals will receive an initial payment from Alfasigma, and will be eligible for additional payments based on certain milestones, totaling over $US 24 million, and receive a 6% royalty (net sales) based on the successful marketing of brilacidin for UP/UPS. The agreement also includes a Right of First Refusal for brilacidin for the treatment of more extensive forms of inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn’s disease, and a right of first negotiation for brilacidin in other gastrointestinal indications. [3]
Innovation Pharmaceuticals, in June 2019, entered into an agreement with Bio-Images Drug Delivery (BDD) Pharma, for the development of tablets for targeted oral delivery of brilacidin to the colon. These tablets will be developed by utilising BDD pharam's proprietary, multi-core timed-release OralogiK™ technology that employs controlled erosion of a time-dependent barrier layer during small intestine transit to provide effective colon targeting. As per the agreement terms, BDD will provide further expertise and resources by collaborating with the Innovation Pharmaceuticals to accelerate initiation of clinical trials.
[4]
In July 2018, Innovation Pharmaceuticals entered into a drug product manufacturing contract with CoreRx to formulate and package brilacidin into granular form in unit dose sachets. The convenient, portable, quick-mixing “instant” brilacidin sachets will be used in clinical trials conducted to treat severe oral mucositis (WHO Grade ≥ 3) in head and neck cancer patients receiving chemoradiation therapy. [5]
In October 2021, Innovation Pharmaceuticals announced that in collaboration with the US government scientists, in vitro studies of brilacidin in 20 acutely infectious viruses including Ebola, Marburg, Nipah, West Nile and Zika [6] .
In November 2014, Cellceutix reported that it has entered into an agreement with a division of one of the largest US pharmaceutical companies to test whether the use of brilacidin as a component of certain implanted devices can prevent infection. The material transfer agreement does not include the pharmaceutical use of brilacidin for the treatment of infections or other diseases. The final contract is subject of brilacidin getting approved by the US FDA [7] .
Cellceutix reported in February 2014 that it had selected Dr. Reddy's Custom Pharmaceutical Services for the formulation of brilacidin for use in ophthalmic and otitis infections [8] .
In April 2013, PolyMedix filed for Chapter 7 bankruptcy with the Bankruptcy Court for the District of Delaware. In August 2013, Cellceutix made a "stalking horse" offer for the purchase of PolyMedix's assets, following a due diligence process. The asset purchase agreement was approved by the Bankruptcy Court for the District of Delaware in September 2013, which involved a cash payment of $US2.1 million and 1.4 million shares of Cellceutix stock; none of PolyMedix's debt was assumed by Cellceutix [9] .
To design compounds like brilacidin, PolyMedix licensed a proprietary computational drug design technology developed at the University of Pennsylvania.
Key Development Milestones
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 [10] .
Innovation Pharmaceuticals announced that formulation development plans include foam and/or gel for the treatment of ulcerative proctitis/ulcerative proctosigmoiditis (Innovation Pharmaceuticals pipeline, February 2021) [11] .
COVID-2019 infections
In July 2021, Innovation Pharmaceuticals completed a phase II trial which evaluated the efficacy and safety of brilacidin in hospitalised patients with COVID-2019 infections (NCT04784897; IPI-BRIc-201). The primary endpoint was time to sustained recovery through day 29, using a clinical status ordinal scale based on that used in the series of National Institute of Allergy and Infectious Diseases (NIAID) Adaptive COVID-19 Treatment Trials (ACTTs). The randomised, double-blind, placebo-controlled trial initiated in February 2021 completed enrolment of 120 patients in the US and Russia, in early June 2021. Earlier in December 2020, US FDA approved Investigational New Drug application (IND) for initiation of phase II trial for brilacidin in the patients with moderate to severe COVID-2019 infection. In November 2020, Innovation Pharmaceuticals announced receipt of the written feedback from the US Food and Drug Administration (FDA) for the phase II trial of brilacidin, for the treatment of hospitalised patients with COVID-2019 infections. The FDA response completes the Pre-Investigational New Drug (Pre-IND) process. In October 2020, the US FDA confirmed request of Innovation Pharmaceuticals for the pre-IND meeting. In the meeting, the company will seek regulatory guidance on the randomised, double-blind, placebo-controlled phase II trial from the agency. The multicentre trial is designed to enroll 120 patients. The active and placebo arms of the trial will recruit approximately 60 patients respectively. Earlier in the similar week, Innovation Pharmaceuticals had submitted a application, requesting the meeting. In November 2020, Innovation Pharmaceuticals announced the submission of an overseas clinical trial application to the governing health agency to proceed with initiation of a phase II trial of intravenous brilacidin for the treatment of hospitalised patients with COVID-2019 infections. The company also intends to submit an IND application to the US FDA for the same trial. As of April 2021, upon recently completing a scheduled review of interim safety data from the trial, an independent Data Monitoring Committee (DMC) recommended increasing the dosing regimen of brilacidin from three days to five days of treatment, which will maximise the therapeutic benefits and provide a comparison with five-day remdesivir. The longer duration of systemic brilacidin exposure at a level that can strongly suppress SARS-CoV-2 virus replication, and associated symptoms, and thus maximize therapeutic benefits. The last patient follow-up visit occurred on July 2021 [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] . In June 2022, the company released efficacy data from the trial [25] .
In November 2021, the company announced compassionate use of brilacidin, for the treatment of extremely critically-ill patients. Compassionate use cases comprised brilacidin being administered over a longer duration (up to 10 days) than in the phase II COVID-19 trial (3 and 5 day dosing), with some patients also receiving higher and more frequent dosing (two doses every 24 hours) [26]
In January 2021, the US FDA granted fast track designation for brilacidin for the treatment for COVID-19 infections [27] .
In March 2023, Innovation Pharmaceuticals released in vitro preclinical data [28]
In December 2022, Data from preclinical study were released by Innovation Pharmaceuticals [29] .
In October 2022, pharmacodynamics data from a preclinical study were released by Innovation Pharmaceuticals [30] .
In September 2020, Innovation Pharmaceuticals released preclinical data for brilacidin, in combination with remdesivir [see AdisInsight drug profile 800043325] in a human lung cell line for COVID-2019 infections. Brilacidin exhibited an inhibitory effect on SARS-CoV-2, as well as different types of alphaviruses, in cell culture [31] .
In March 2021, Innovation Pharmaceuticals released preclinical data for brilacidin from cell culture assays in COVID-2019 infections [32] .
In August 2020, Innovation Pharmaceuticals released preclinical data for brilacidin from antiviral assays in COVID-2019 infections [33] [34] .
In July 2020, Innovation Pharmaceuticals released data evaluating from the ongoing laboratory testing being conducted at a U.S. Regional Biocontainment Laboratory (RBL). Based on the results the company is considering conducting in vitro testing combining Brilacidin with Remdesivir [35] .
In August 2021, Innovation Pharmaceuticals reported that, in preclinical studies, brilacidin demonstrated potential activity against endemic H-CoV strains (OC43, 229E, NL63) and inhibited different H-CoV strains which showed that brilacidin as a pan-coronavirus agent [36] .
In June 2022, Innovation Pharmaceuticals reported results from in vitro testing conducted in collaboration with National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) [25]
As of July 2020, ongoing laboratory testing conducted at a US Regional Biocontainment Laboratory (RBL), and at a Public Health Research Institute, supported Brilacidin’s antiviral ability to safely inhibit SARS-CoV-2 in both human and animal cell lines. The in vitro neutralisation experiments (with a pseudotyped virus), binding experiments (using isolated SARS-CoV-2 Spike protein) and studies in lung epithelial cell line conducted at the RBL supported antiviral activity of brilacidin against SARS-CoV-2. In June 2020, Innovation Pharmaceuticals released the results from the preclinical studies of brilacidin conducted at a US RBL in human lung cell lines for the treatment of COVID-2019 infections. The company also intends to seeking FDA guidance for a planned COVID-19 clinical study. Earlier in May 2020, Innovation Pharmaceuticals announced that the Lab testing 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 the drug'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 [37] [38] [39] . As of July 2020, manufacturing preparation for COVID-19 infections are underway [40] [41] .
Innovation Pharmaceuticals in November 2020, reported data from in vitro studies, whereby brilacidin demonstrated similar inhibition againsut two strains of SARS-CoV-2. The data indicated that brilacidin may not be susceptible to development of resistance due to mutaions in SARS-CoV-2 [19] . In May 2020, Innovation Pharmaceuticals released preclinical data for brilacidin from antiviral assays in COVID-2019 infections. Brilacidin showed broad spectrum antiviral activity and potent and consistent inhibition in vitro against coronaviruses, alphaviruses and bunyaviruses. In July 2021, the company presented the in vitro antiviral data at the American Society of Virology’s 40th Annual Meeting (ASV-2021) [42] [14] [43] [39] .
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 combination; antiviral, immune/anti-inflammatory, and antimicrobial) anti-COVID-19 therapeutic candidate [2] [44] [45] [46] .
Coronavirus infections
In January 2021, Innovation Pharmaceuticals announced that brilacidin in preclinical testing inhibited the Washington and Italian strains of the coronavirus [47] . In November 2020, Innovation Pharmaceuticals reported that brilacidin showed potent in vitro inhibition of multiple strains of endemic human coronaviruses (H-CoVs). The company also intends to conduct additional in vitro and in vivo studies on multiple coronaviruses with the aim of developing brilacidin as pan-coronavirus therapeutic [48] .
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 [49] [50] .
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 [51] .
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 [52] [53] . 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 [54] [55] [56] [57] [58] [59] .
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 [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] .
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 [77] .
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 [78] [79] [80] [81] [82] .
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 [83] [84] [85] . 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 [86] [87] . After completion of the phase I trial, PolyMedix intended to hold discussions with the FDA concerning further development of the drug in the US [88] .
In March 2010, PolyMedix released final results for its phase Ib trial of brilacidin that assessed the safety of repeated dosing [89] . 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) [90] [91] [92] [93] [94] [95] .
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 [96] . 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 [97] [98] .
In December 2014, the US FDA granted the qualified infectious disease product (QIDP) designation to brilacidin for the treatment of ABSSSI [99] . 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 [100] [101] [68] .
Monkeypox
In August 2022, Innovation Pharmaceuticals announced that, through a collaboration with National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), brilacidin is planned to be evaluated in Monkeypox. To establish potential proof-of-concept, in vitro testing will be conducted initially in orthopoxviruses1 (poxviruses) related to monkeypox, such as vaccinia and cowpox [102] .
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 [103] .
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 [104] [105] .
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 [106] [107] .
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 [108] [109] [110] .
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 [111] [112] . The randomised 1:1, parallel, double-blind trial was initiated in August 2014 and enrolled 61 patients in the US [113] [114] [115] [109] [116] [117] [118] [52] [119] [120] [121] [122] .
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 [64] . Cellceutix submitted IND application with the US FDA in September 2014 [65] . The company received the final IND-enabling toxicology report for brilacidin in this indication in August 2014 [123] . 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 [61] [7] [124] [122] .
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 [60] [125] .
Brilacidin-OM reduced the occurrence of severe ulcerative oral mucositis by more than 94% as compared with placebo in an animal model [126] . 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 [127] . Brilacidin has also shown positive results in a 28-day acute radiation model, and a 35-day fractionated radiation model [128] . 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 [101] [129] .
Cellceutix has filed an application with the US FDA in December 2013 requesting orphan drug status for brilacidin in this indication [130] .
Ulcerative proctitis/colitis
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 [131] [132] [133] [134] [50] [135] .
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) [136] . 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 [137] [138] [139] [140] [141] [60] [53] [142] [143] [144] [52] [145] [11] [146] . 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 [147] [148] .
In November 2014, Innovation Pharmaceuticals announced that IND-enabling studies of brilacidin in ulcerative colitis are underways [7] [146] .
Innovation Pharmaceuticals plans to conduct gastroenterological studies of brilacidin as foam and tablet formulations [141] .
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 [149] .
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 [101] . 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 [64] .
Other indications
In October 2021, Innovation Pharmaceuticals announced that preclinical studies are underway in Marburg virus disease, Nipah virus infection, West Nile virus infection, Zika virus infection in the US [6] .
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 [150] [151] . 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) [152] [153] .
Innovation Pharmaceuticals plans to initiate clinical trials of brilacidin for the treatment of atopic dermatitis, acne and hidradenitis suppurativa [116] [140] [141] [154] . 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 [155] .
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 [156] .
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 [157] . 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 [53] .
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 [10] . 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 [158] .
Innovation Pharmaceuticals is also conducting preclinical studies of brilacidin for otitis media and otitis externa [159] . The company will develop its new room temperature-stable formulation for the treatment of otitis media [10] . 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 [119] . 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.
Financing information
In June 2020, Innovation Pharmaceuticals in collaboration with the US Regional Biocontainment Laboratory (RBL) submitted a federal grant application proposing to evaluate brilacidin’s potential as a pan-coronavirus therapeutic, with possible extension into other viruses based on the preclinical results in COVID-2019 infections (see above) [38] [160] .
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 [161] .
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 [162] .
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 [163] .
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 [164] .
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 [129] [165] .
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 [166] .
Patent Information
As of June 2023, Innovation Pharmaceuticals submitted a patent application to the USPTO for use of Brilacidin in fungal diseases [167] .
In June 2023, Innovation Pharmaceuticals received a notice of allowance from the United States Patent and Trademark Office for a patent application covering, “Arylamide Compounds For Treatment Of Viral Infections.” The protection will be valid till 2041 [167] .
In June 2023, the United States Patent and Trade Office (USPTO), granted US patent no. US 16 991 812 titled, “Host Defense Protein (HDP) Mimetics for Prophylaxis and/or Treatment of Inflammatory Diseases of the Gastrointestinal Tract." The protection will be valid till 2036 [167] .
In February 2019, Innovation Pharmaceuticals reported that the USPTO had granted patent number 10 206 894, which covers methods for treating and/or preventing mucositis with one or more compounds, or pharmaceutically acceptable salts [168] .
Innovation Pharmaceuticals reported that the USPTO granted the “Issue Notification” of a new patent (projected US patent number 10 166 232) that covers brilacidin in the form of a pharmaceutical composition containing water and Tris-buffered saline. The patent also covers Brilacidin in combination with additional therapeutic agents, including an antibiotic, an anti-inflammatory agent, an anesthetic agent, an anti-allergic agent, an acetylcholine blocking agent, an adrenergic agonist, a beta-adrenergic blocking agent, an anti-glaucoma agent and an anti-hypertensive agent. This patent builds on the “Notice of Allowance” covering oral, buccal and sublingual pharmaceutical compositions of brilacidin [169] .
In November 2018, the USPTO issued a 'Notice of Allowance' to Innovation Pharmaceuticals, covering oral, buccal, and sublingual pharmaceutical compositions of brilacidin, including liquid compositions, such as rinses. Earlier, US patents with patent numbers 8 802 683, 9 155 738, 9 457 027 and 9 795 575 were granted [170] .
Innovation Pharmaceuticals, in December 2017, was granted a European patent by the European Patent Office for brilacidin for the prevention and control of oral mucositis. Similar patents were granted in the US, Asia (Japan, Taiwan, China), Australia and South Africa, all the patents are valid through 2032. The candidate also has pending patent applications in Russia and South Korea [171] .
In September 2009, the University of Pennsylvania was issued US Patent No. 7,590,517 entitled 'Methods, Systems, and Computer Program Products for Computational Design of Amphiphilic Polymers,' which provides protection for the underlying process and implementation of two proprietary computational methodologies, PACE™ (Proteomic Assisted Computational Engine) and GOLDYN™ (Global Optimization of Long-time Dynamics force field). The two methodologies were used by PolyMedix in its development of defensin mimetic antibiotic compounds, including brilacidin [172] .
PolyMedix was issued the US Patent No. 7,173,102 entitled 'Facially Amphiphilic Polymers as Anti-Infective Agents' in February 2007. The patent claims compositions of matter for facially amphiphilic polymers and oligomers. Also claimed are antimicrobial material compositions, methods of killing micro-organisms and processes of producing antimicrobial surfaces [173] .
Drug Properties & Chemical Synopsis
- Route of administration IV, Ophthalmic, Otic, PO, Rectal, Topical
- Formulation Controlled release, Enema, Infusion, Liquid, unspecified
- Class Amides, Anti-infectives, Anti-inflammatories, Antiacnes, Antibacterials, Antivirals, Foot disorder therapies, Guanidines, Peptidomimetics, Pyrimidines, Pyrrolidines, Skin disorder therapies, Small molecules
- Target Cell membrane structure; Type 4 cyclic nucleotide phosphodiesterase; Virus internalisation
- Mechanism of Action Cell membrane permeability enhancers; Cell membrane structure modulators; Immunomodulators; Type 4 cyclic nucleotide phosphodiesterase inhibitors; Virus internalisation inhibitors
-
WHO ATC code
A01A (Stomatological Preparations)
A07E (Intestinal Antiinflammatory Agents)
D03 (Preparations for Treatment of Wounds and Ulcers)
D10 (Anti-Acne Preparations)
D11 (Other Dermatological Preparations)
J01X (Other Antibacterials)
J05A-X (Other antivirals)
S02A (Antiinfectives)
-
EPhMRA code
A1 (Stomatologicals, Mouth Preparations, Medicinal Dentifrices etc)
A7E (Intestinal Anti-Inflammatory Agents)
D10 (Anti-Acne Preparations)
D11 (Other Dermatological Preparations)
D3 (Wound Healing Agents)
J1X (Other Antibacterials)
J1X1 (Glycopeptide antibacterials)
J5 (Antivirals for Systemic Use)
S2A (Otic Anti-Infectives)
- Chemical name N4,N6-bis(3-(5-guanidinopentanamido)-2-((R)-pyrrolidin-3-yloxy)-5-(trifluoromethyl)phenyl)pyrimidine-4,6-dicarboxamide tetrahydrochloride
- Molecular formula C40 H54 Cl4 F6 N14 O6
- SMILES C1=C(C=C(C(=C1NC(=O)CCCCNC(=N)N)OC1CCNC1)NC(=O)C1=CC(=NC=N1)C(=O)NC1=CC(=CC(=C1OC1CCNC1)NC(=O)CCCCNC(=N)N)C(F)(F)F)C(F)(F)F.Cl
-
Chemical Structure
- CAS Registry Number 1224095-98-0
Biomarkers Sourced From Trials
| Indication | Biomarker Function | Biomarker Name | Number of Trials |
|---|---|---|---|
|
abscess |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
COVID-19 respiratory infection |
Outcome Measure |
Tumor necrosis factor alpha (TNF-alpha) Lactate dehydrogenase (LDH) Interleukin-6 (IL-6) Interleukin-18 (IL-18) Interleukin-10 (IL-10) Ferritin D-dimer Cardiac Troponin I C-reactive protein (CRP) |
|
|
methicillin-resistant Staphylococcus aureus infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
post-traumatic infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
postoperative infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
skin and soft tissue infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
staphylococcal infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
streptococcal infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
|
|
wound infections |
Eligibility Criteria |
T-cell surface antigen CD4 C-reactive protein (CRP) |
Biomarker
| Drug Name | Biomarker Name | Biomarker Function |
|---|---|---|
| Brilacidin - Alfasigma/Innovation Pharmaceuticals | C-reactive protein (CRP) | Eligibility Criteria, Outcome Measure |
| Cardiac Troponin I | Outcome Measure | |
| D-dimer | Outcome Measure | |
| Ferritin | Outcome Measure | |
| Interleukin-10 (IL-10) | Outcome Measure | |
| Interleukin-18 (IL-18) | Outcome Measure | |
| Interleukin-6 (IL-6) | Outcome Measure | |
| Lactate dehydrogenase (LDH) | Outcome Measure | |
| T-cell surface antigen CD4 | Eligibility Criteria | |
| Tumor necrosis factor alpha (TNF-alpha) | Outcome Measure |
Development Status
Summary Table
| Indication | Qualifier | Patient Segment | Phase | Countries | Route / Formulation | Developers | Event Date |
|---|---|---|---|---|---|---|---|
| Acne | - | - | No development reported (Preclinical) | USA | Topical / unspecified | Innovation Pharmaceuticals | 28 Aug 2022 |
| Alphavirus infections | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 27 May 2021 |
| Atopic dermatitis | Eczema | - | No development reported (Preclinical) | USA | Topical / unspecified | Innovation Pharmaceuticals | 28 Aug 2022 |
| Bunyavirus infections | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 27 May 2021 |
| COVID 2019 infections | - | - | Phase II | Russia, USA (fast track) | IV / unspecified | Innovation Pharmaceuticals | 22 Feb 2021 |
| COVID 2019 infections | - | Prevention | Preclinical | USA | IV / unspecified | Innovation Pharmaceuticals | 04 Aug 2020 |
| Coronavirus infections | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 30 Nov 2020 |
| Diabetic foot ulcer | - | - | No development reported (Preclinical) | USA | unspecified / unspecified | Innovation Pharmaceuticals | 28 Aug 2018 |
| Ebola virus infections | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 25 Oct 2021 |
| Hidradenitis suppurativa | - | - | No development reported (Preclinical) | USA | Topical / unspecified | Innovation Pharmaceuticals | 28 Aug 2022 |
| Inflammatory bowel diseases | - | In volunteers | No development reported (I) | United Kingdom | PO / Controlled release | Innovation Pharmaceuticals | 28 Mar 2023 |
| Inflammatory bowel diseases | - | - | No development reported (Preclinical) | USA | PO / Controlled release | Innovation Pharmaceuticals | 28 Feb 2023 |
| Intestinal infections | - | - | Discontinued (Preclinical) | USA | PO / unspecified | Innovation Pharmaceuticals | 08 Jan 2018 |
| Marburg virus disease | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 25 Oct 2021 |
| Nipah virus infections | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 25 Oct 2021 |
| Ophthalmic infections | - | - | Discontinued (Preclinical) | USA | Ophthalmic / unspecified | Innovation Pharmaceuticals | 08 Jan 2018 |
| Otitis | - | - | No development reported (Preclinical) | USA | Otic / unspecified | Innovation Pharmaceuticals | 28 Feb 2018 |
| Skin and soft tissue infections | Acute bacterial skin and skin structure infections due to Staphylococcus aureus Acute bacterial skin and skin structure infections due to Staphylococcus aureus (including MRSA) and Streptococcus pyogenes | - | Phase II | Canada, Russia, USA, Ukraine | IV / Infusion | Innovation Pharmaceuticals | 18 Feb 2014 |
| Stomatitis | In patients with head and neck cancer undergoing chemoradiation | Prevention | Phase II | USA (fast track) | Topical / Liquid | Innovation Pharmaceuticals | 14 Aug 2014 |
| Ulcerative colitis | - | - | Discontinued (Preclinical) | USA | Topical / unspecified | Innovation Pharmaceuticals | 08 Jan 2018 |
| Ulcerative proctitis | - | - | Phase II | USA | Rectal / Enema | Innovation Pharmaceuticals | 15 Jun 2016 |
| Ulcerative proctitis | - | In volunteers | No development reported (I) | USA | PO / Controlled release | Innovation Pharmaceuticals | 28 Feb 2023 |
| West Nile virus infections | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 25 Oct 2021 |
| Wounds | Non-infected | - | No development reported (Preclinical) | USA | unspecified / unspecified | Innovation Pharmaceuticals | 28 Jun 2018 |
| Zika virus infection | - | - | Preclinical | USA | unspecified / unspecified | Innovation Pharmaceuticals | 25 Oct 2021 |
Priority Development Status
| Type | Region | Indication |
|---|---|---|
| Fast Track | USA | COVID 2019 infections; Stomatitis |
| Qualified Infectious Disease Product | USA | Skin and soft tissue infections |
Commercial Information
Involved Organisations
| Organisation | Involvement | Countries |
|---|---|---|
| PolyMedix | Originator | USA |
| Innovation Pharmaceuticals | Owner | USA |
| Alfasigma | Licensee | World |
| University of Pennsylvania | Technology Provider | USA |
| Bio-Images Drug Delivery | Collaborator | United-Kingdom |
| Dr Reddys Laboratories | Collaborator | India |
Licensing Availability
| Licensing Organisation | Available Indication | Available Phase | Region | Date |
|---|---|---|---|---|
| Innovation Pharmaceuticals | COVID 2019 infections | Unspecified | - | 20 Apr 2020 |
Scientific Summary
-
Adverse Events
Frequent:
Paraesthesia
Occasional: Blood platelet disorders; Hypertension; Numbness
Pharmacokinetics
Phase II:
Interim results from a phase II study in four patients with ulcerative proctitis, treated with brilacidin at the lowest dose (50 mg), showed that drug concentrations in plasma, across all time points, were below the lower limit of quantification (i.e., <100 ng/mL), which is consistent with very limited systemic exposure from administration per rectum by enema [154] [144] . Updated interim results from the phase II study in ulcerative proctitis demonstrated that drug concentrations in plasma continued to show limited systemic absorption of brilacidin, with all values registering less than 100 ng/mL for all six patients in Cohort A and averaging approximately 215 ng/mL maximum concentrations across the six patients in Cohort B [137] [148] [146] .
Stomatitis
In a preliminary interim analysis of a phase II trial, all concentrations of brilacidin were below the lower limit of quantification (< 10 ng/mL) in plasma samples from six patients. The randomised, double-blind trial is designed to evaluate the safety and efficacy of brilacidin oral rinse in preventing and controlling oral mucositis in 60 patients with head and neck cancer undergoing chemoradiation [118] [122] .
Clinical
In pooled results for two randomised, placebo-controlled, multiple-dose phase I trials of intravenous brilacidin in a total of 77 healthy male volunteers, the terminal elimination half life varied between 16.6 and 23 hours. Pharmacokinetics were dose-dependent [182] .
The pharmacokinetic parameters of IV brilacidin were similar between male and female volunteers in a phase I multiple-dose study [86] .
In a phase I clinical study involving 22 healthy volunteers, simple exponential kinetics were observed, with a distribution and elimination half-life of 1.5 and 15 hours, respectively. Peak plasma levels were consistently found to be about 15 times the dose, so that 0.18 mg/kg resulted in a mean Cmax of 2.7 µg/mL, and the 0.54 mg/kg dose had a mean Cmax of 8 µg/mL. Pharmacokinetic modelling with this data suggested that a single daily dose of 0.18 mg/kg would provide steady-state plasma levels exceeding 2 µg/mL for 12 hours daily and exceeding 1 µg/mL continuously. The same dose twice daily, or a once-daily dose of 0.4 mg/kg, would provide plasma levels exceeding 2 µg/mL for 16 hours and exceeding 1 µg/mL continuously from the first day of treatment [97] .
The mean plasma half-life of intravenous brilacidin was 23 hours, according to results from a phase I trial (PMX63-103) in 16 healthy volunteers. A loading dose of 1mg/kg was followed by 0.35mg/kg daily on days 2-14 [84] . Urinary excretion accounted for <1% of elimination; in males and females, respectively, 0.258 and 0.219mg of drug was recovered unchanged in urine [85] .
Preclinical
efficacy in the neutropenic mouse thigh burden with brilacidin against MRSA and MSSA strains of Staphylococcus aureus was demonstrated to be highly correlated with reaching minimal inhibitory concentration (MIC) levels of free compound in plasma. Full efficacy was achieved with MSSA and MRSA when plasma C0 values of free brilacidin reached MIC levels (0.7 to 1.2 µg/ml, respectively), and AUC values of free brilacidin reached 3 000 to 6 000 h*ng/ml, respectively [185] .
At maximally efficacious doses in preclinical infection models, pharmacokinetic parameters at therapeutic doses were comparable to human subjects at doses more than 0.18 mg/kg [97] .
Following a single 2mg/kg intravenous dose of [14C]-brilacidin, 40.17% and 25.47% of radioactivity was found in faeces of male and female rats, respectively. This indicates that the bile and/or the gut mucosa may be a main route of elimination. Renal excretion is not a significant elimination pathway [85] .
In a study involving a simulated gastric fluid model, brilacidin was minimally degraded across four hours, indicating that orally formulated brilacidin was not susceptible to rapid breakdown in the stomach. These results suggested the likelihood of developing an oral formulation of the drug for the effective treatment of inflammatory bowel disease [51] .
Preliminary top-line results demonstrated that no quantifiable brilacidin concentrations in blood at any timepoint across treatment cohorts and shows containment of Brilacidin within the target location [49] [50] .
Adverse Events
Skin and soft tissue infections
Top-line data from a phase IIb trial in an intent-to-treat population, demonstrated that three dosing regimens of brilacidin was safe and generally well tolerated in patients with acute bacterial skin and skin structure infections (ABSSSI). Six severe adverse events, unrelated to the drug, were reported. Adverse events appeared to be exposure-related. Aside from mild, transient numbness and tingling (for which no patient discontinued treatment), the overall adverse event rates were under 10% in each treatment group (low, medium and high doses of brilacidin and daptomycin). In 3.8% (n = 6/160) of patients treated with brilacidin, transient increases in systolic blood pressure were observed; of these patients, half (n = 3) were in the high-dose group. Previous interim results also showed a case of increased platelets in the low dose group. In this double-blind trial, 215 patients were randomised to one of three dosing regimens of brilacidin (0.4 mg/kg on day 1 then 0.30 mg/kg [low], 0.75 mg/kg on day 1 then 0.35 mg/kg [medium] or 1.0 mg/kg on day 1 then 0.35 mg/kg [high]) once daily for 5 days followed by placebo for 2 days, or daptomycin once daily for 7 days. An approximately 25% of 215 patients were recruited into each treatment arm [78] [179] [181] .
Ulcerative proctitis
Phase II
Interim results from the phase II CTIX-BRI-206 proof-of-concept trial in ulcerative proctitis demonstrated that brilacidin was safe and well tolerated by patients in both cohorts A and B and all patients maintained stable vital signs. A total of 16 adverse events in six patients were reported, none of which were related to the study drug. No serious adverse events were reported [137] [148] [141] [146] .
Stomatitis:
Brilacidin 45 mg/15 ml oral rinse, for prevention and control of stomatitis, was generally safe and well-tolerated in a phase II trial in patients with head and neck cancer undergoing chemoradiation. Safety findings were typical for patients with this indication and all treated patients reported at least one treatment-emergent adverse event (TEAE). At least one serious adverse event (SAE) was reported in 13 patients, 8 from the brilacidin group, and 5 from the placebo group, of the TEAE categorised as SAEs. SAEs were not related to brilacidin treatment. There was no death because of the SAEs. The randomised 1:1, parallel-group, double-blind trial enrolled 61 patients. The oral rinse of brilacidin or placebo was self-administered by patients for three times daily across 7 consecutive weeks in the trial [115] [118] [122] .
Healthy volunteers
Phase I
in pooled results for two randomised, placebo-controlled phase I trials of intravenous brilacidin in a total of 77 healthy male volunteers, the most common adverse events were paraesthesia and increases in blood pressure and heart rate, all of which were transient and required no treatment. No gastrointestinal or renal effects were observed. Brilacidin showed an unremarkable safety profile between 0.1 and 0.3mg/kg once-daily dosing. Increasing the frequency of dosing from once- to twice-daily did not appear to improve the safety profile at comparable dose levels [182] .
The most frequently reported adverse event in a phase I, multiple-dose trial of brilacidin was transient paraesthesias of the lips, face and fingers. In this randomised, double-blind study, 20 male and female volunteers received a loading dose (1mg/kg) of intravenous brilacidin followed by daily dosing (0.35mg/kg) for up to 14 days. The paraesthesias did not worsen over the study period and most cases resolved after withdrawal of brilacidin. Several volunteers were withdrawn from the study after 9-13 days' treatment due to hypertension and increased heart rate, and one subject experienced reversible atrial fibrillation. A few cases of transient elevations in liver enzymes were noted but the changes were not clinically significant [86] . Based on these results, it was concluded that once-daily dosing of brilacidin for 5 days is an appropriate regimen [84] .
Brilacidin was generally well tolerated whether administered every 12h or every 24h in a phase Ib study in healthy volunteers. In the randomised, placebo-controlled study, the maximum tolerated dose of brilacidin for investigation in phase II studies was found to be 3.0 mg/kg (0.3 mg/kg every 12 hours or 0.6 mg/kg every 24 hours). No clinically significant adverse effects at therapeutic dosages were observed [91] [93] .
In a phase Ib study of brilacidin, a dose-limiting toxicity was found at the higher dosages and consisted of paraesthesias. These usually beginning in the oral area and extension to the face, scalp, extremities, upper thorax, and/or perineum, lasting from hours to days. In all cases the effects were temporary and resolved without treatment. Transient increases in ALT and AST were observed in some subjects at higher doses and in all cases resolved without treatment after completion of the study. Healthy volunteers (n = 56) were divided into 8 cohorts and received up to 5 doses of either brilacidin or placebo. The doses ranged from 0.1 mg/kg to 0.6 mg/kg per day and were administered as a single one-hour infusion every 24 or 48 hours. Dosing continued until a threshold was reached where more than one volunteer in a cohort tolerated fewer than 5 doses. There were minimal clinically relevant adverse events at 0.2 mg/kg (total dose of 1.0 mg/kg), and there was no early termination of dosing until the 0.4 mg/kg level. At the 0.5 and 0.6 mg/kg doses (up to 2.5 and 3.0 mg/kg total doses, respectively), the syndrome of subjective effects became more prominent. As also seen in the previous Phase 1a clinical study, there were no objective correlates or clinical measurements associated with the sensations. Five of ten subjects intended to receive 2.5 mg/kg or more total dose tolerated that amount. The data confirmed that a total dose of 3.0 mg/kg, given as 5 doses of 0.6 mg/kg once-daily, was the limiting dosage in this study [94] [87] .
In a phase I clinical study involving 22 healthy volunteers, brilacidin at doses 0.54 mg/kg and above resulted in paresthesias, usually beginning in the oral area and extension to the face, scalp, extremities, upper thorax, and/or perineum. The degrees of extension appeared to correlate with dosage increase, with symptoms lasting from hours to days. No adverse events were classified as serious or severe; however, mild to moderate symptoms suggested that dose escalation could be halted to 2.5 mg/kg [97] [87] .
Animal toxicology
In preclinical studies, brilacidin at 12 and 24 mg/kg/day bid, given as an IV infusion was well-tolerated. Transient reduction in feed consumption and body weight loss was observed in the high dose group. No other acute brilacidin-related effects were observed [187] .
Studies on peripheral nerve function in rats showed that the effect of brilacidin is of a pharmacological nature, without neurotoxicity [191] .
Preliminary top-line results from the phase I trial demonstrated that the trial met its primary endpoints and brilacidin delayed release was well tolerated across all treatment cohorts with no serious adverse events. Two volunteers on brilacidin delayed release and two on placebo experiences atleast one adverse events of mild intensity and not related to study treatment [49] [50] .
Pharmacodynamics
Summary
Brilacidin demonstrated in vivo efficacy in the mouse subcutaneous abscess (MSCA) and rat granuloma pouch (RGP) infection models of Staphylococcus aureus skin infections. In the MSCA model, brilacidin demonstrated log CFU reductions of 1.3 - 2.3 for IV dosing regimens (both once and twice daily) between 10-20 mg/kg as compared to untreated controls. In the RGP model, brilacidin effected log CFU reductions in pouch fluid of 1.1-2.5 following single IV doses of 4-20 mg/kg and up to a 5 log reduction at 10 mg/kg twice daily (within 6 hrs of administration) [184] .
Brilacidin demonstrated robust efficacy against MSSA and MRSA in a mouse thigh burden model, and against MSSA in a rat thigh burden model and a mouse peritonitis model [187] .
Brilacidin demonstrated activity in vitro against the New Delhi metallo-beta-lactamase-1 (NDM-1) drug resistant strain of Klebsiella pneumonia [183] .
In a chinchilla model of otitis media, brilacidin treatment greatly reduced Streptococcus pneumonia bacterial counts, with no toxic effects [8]
Brilacidin suppressed various pro-inflammatory mediators (such as TNF-α, IL-1β, IL-8, IL-6, MMP-9, MCP-1). Preclinical studies showed dose-dependent inhibition of PDE4B2 and PDE3A, in vitro, with brilacidin treatment. Brilacidin may possess good cell membrane permeability property, based on similar IC50 values against both PDE4 (biochemical) and cytokine release in cell-based assays. Localised clinical administration allowed brilacidin concentrations that markedly exceed in vitro IC50 values, thus, providing for increased concentrations of cAMP. The overall effect of Brilacidin’s ability to modulate cAMP levels supports its potential to treat a number of chronic, autoimmune and inflammatory diseases related to issues of innate immunity, such as inflammatory bowel disease, atopic dermatitis and others [175] .
In an acute radiation model in hamsters (n=10), brilacidin (at the three highest doses) significantly reduced peak mucositis scores and daily mucositis scores on 9 to 10 of the 10 evaluation days when stomatitis was evident (p<0.001 vs vehicle). At the three highest doses, brilacidin reduced the number of animal days with ulceration by ≅90%; from 42% in vehicle-treated group to <5% in the active treatment groups (p<0.001). Brilacidin was dosed as a topical rinse three times daily, at 0.03, 1.0, 3.0 or 10.0mg/mL for 28 days, following a single dose of radiation to the buccal cheek pouch (40 Gy). In a fractionated radiation model in hamsters, brilacidin significantly reduced daily mucositis scores prior to peak stomatitis, and during the remaining treatment period (p<0.001 vs vehicle). Brilacidin reduced the number of animal days with ulceration by ≅94%; from 55% in vehicle-treated animals to 3.3% (p<0.001). Radiation was administered at 7.5 Gy/dose on days 0, 1, 2, 3, 6, 7, 8 and 9, targeting the left buccal pouch mucosa. Brilacidin 3mg/mL was dosed three times for 35 days [128] .
Treatment of non-infected wounds with brilacidin for 5 days decreased the time to wound healing, compared with untreated controls, in a diabetic rat model. Complete reduction of the wound area was observed in brilacidin-treated animals [158] .
Results from the preclinical studies showed that brilacidin converted CAS from a fungistatic into a fungicidal drug, enabling it to overcome both drug resistance and biofilm formation, in cell culture, in Aspergillus fumigatus (A. fumigatus). Brilacidin exerted, to a lesser degree, synergistic effects with VOR in A. fumigatus. Further in vitro testing showed brilacidin synergized with CAS in C. albicans, C. auris and C. neoformans. In an A. fumigatus immunosuppressed mouse model in invasive pulmonary aspergillosis, brilacidin plus CAS cleared infection in the lungs by almost 95 percent, compared to ~50 percent when each compound was administered individually. Brilacidin also showed in vitro an additive inhibitory effect when combined with POSA in several species of mucorales, the main etiological agents of mucormycosis, commonly referred to as black fungus [30] .
In in-vitro studies Brilacidin is exhibiting promising antifungal activity against many of these priority pathogens, including C. neoformans, A. fumigatus, C. albicans, Mucorales, Fusarium, Scedosporium spp., Lomentospora proflicans and C. krusei. New in vivo data in an A. fumigatus murine fungal keratitis model showed Brilacidin reduced fungal burden and disease severity, while also improving corneal thickness compared to control. Brilacidin-treated corneas harbored almost no viable fungus, suggesting the compound suppressed fungal proliferation within the cornea [29] .
COVID-2019 infections
In preclinical studies conducted in human lung epithelial cell lines, brilacidin exhibited a statistically significant (p < 0.0001) and potent inhibitory effect on SARS-CoV-2 virus, reducing viral load by 95% and by 97%, compared to control, at two therapeutic concentrations tested. Based on a CC50 value, the drug was also shown to be non-cytotoxic in the lung cell line. Brilacidin, in an in vitro experiment in human kidney cell line expressing hACE2, demonstrated an average of 29% inhibition at 0.1ug/ml and 85% inhibition at 100ug/ml. Earlier in vitro results using VERO cells, reduced the viral titer (load) of SARS-CoV-2 by 75 percent after only 1 hour of preincubation prior to infection at a concentration of 10µM as compared to vehicle control. An earlier 16-hour post-infection experiment, in VERO cells, showed Brilacidin exhibited a dose-dependent reduction in SARS-CoV-2 infectious viral titers.In VERO cells (a monkey kidney cell line), at 16 hours post-infection, treatment with brilacidin demonstrated a dose-dependent reduction in the SARS-CoV-2 infectious viral titers compared with vehicle-alone control (Dimethyl sulfoxide or DMSO) [37] [44] [45] [43] [39]
In vitro
data showed brilacidin exhibited a similarly potent inhibitory effect against SARS-CoV-2 at an even lower concentration in the same human lung epithelial cell line using the previously used assay method (RBL assay; which included brilacidin pre-incubated with virus). Ninety percent inhibition of SARS-CoV-2 at a drug concentration that was one-half lower than previously tested was achieved with brilacidin. The drug exhibited inhibition at a concentration that was similar to that of Remdesivir which again reported 50 percent inhibition of the coronavirus. The lowest concentration of Brilacidin used in the testing to date is well below the clinically-achievable concentration of the drug. The RBL data also supported Brilacidin showing an ability to inhibit viral entry into cells, a highly desirable mechanism of action as it is the first step in the infection process enabling viruses to be targeted outside the cell, whereas remdesivir impacted viral replication only after the host cell has been infected [35] .
Preliminary data in COVID-2019 infections showed that brilacidin’s Selectivity Index (SI) of 426 in a human lung epithelial cell line. Brilacidin’s SI was higher than the SIs of a vast majority of other antiviral drugs being evaluated as COVID-19 treatments. In an experiment in a human lung epithelial cell line, brilacidin, when directly incubated with the live (or wild type) virus, was shown to inhibit the virus by 50% at a mid-nanomolar concentration, while remaining non-cytotoxic to cells at high micromolar concentrations. Additionally, this testing in the human lung cell line showed Brilacidin’s IC90 value to be in the low micromolar range [34] [33] .
In preclinical studies conducted in human lung epithelial cell lines, brilacidin in combination with remdesivir showed a statistically significant and synergistic inhibition of SARS-CoV-2 compared to remdesivir-only treated conditions. Overall viral load was reduced by 99.85 percent in one combination experiment, with remaining virus dropping to near undetectable levels. In other newly conducted studies, brilacidin was shown to inhibit SARS-CoV-2 in a human intestinal epithelial cell line and in primary fibroblast cells obtained from human donors [31] .
Results of preclinical studies showed that brilacidin exerts potent inhibitory effects on SARS-CoV-2 in cell culture by decreasing the viral load in different cell types, including ACE2 positive human lung cells. Importantly, both Washington strain-nCoV/USA-WA1/2020 and Italy strain-Italy-INMI1 in Calu-3 cells showed similar decrease. Brilacidin treatment resulted in a dose-dependent decrease in infectious viral titer with a maximum of 53% inhibition of virus observed. The level of inhibition observed at entry was slightly lower than that observed for cells pre- and post-treated with brilacidin concomitantly. Brilacidin had an inhibitory effect on SARS-CoV-2, potentially by disrupting viral integrity and impairing the virion’s ability to complete the viral entry process [32] .
Antiviral data from the in vitro studies showed brilacidin’s inhibition of SARS-CoV-2 in additional cell lines (Caco-2, primary lung fibroblasts), and brilacidin’s inhibition of alphaviruses, Venezuelan Equine Encephalitis Virus, Eastern Equine Encephalitis Virus and Rift Valley Fever Virus, a bunyavirus [42] .
In preclinical studies, in vitro testing demonstrated that brilacidin inhibited the Omicron (B.1.1.529) and Delta (B.1.617.2) variants of SARS-CoV-2 and also inhibited in vitro the Gamma (P.1) and Alpha (B.1.1.7) variants of SARS-CoV-2. Brilacidin has consistently inhibited all coronaviruses tested, independent of cell type, at generally attainable systemic concentrations [25]
Antimicrobial Activity
Summary
Clinical
In two phase Ib dose-escalation trials, intravenous brilacidin had antibacterial activity against both meticillin-susceptible and meticillin-resistant strains of Staphylococcus aureus (MSSA and MRSA) in blood samples taken from healthy male volunteers who had received brilacidin at doses of 0.1 mg/kg or higher. In these randomised trials, 77 subjects received either placebo or brilacidin at doses ranging from 0.1-0.6 mg/kg/day, administered every 12h, 24h or 48h [91] [93] . Bactericidal activity in serum against MSSA and MRSA strains was observed at single doses of 0.1-0.3 mg/kg [182] .
In antimicrobial assays following brilacidin treatment, bacteriostatic and bactericidal activity against methicilin-sensitive Staphylococcus aureus (S. aureus) and MRSA strains were achieved at doses at or above 0.2 mg/kg, and largely correlated with those established in normal medium and in experimental animal studies. Healthy volunteers (n = 56) were divided into eight cohorts and received up to 5 doses of either brilacidin or placebo. The doses ranged from 0.1 mg/kg to 0.6 mg/kg per day and were administered as a single 1h infusion every 24 or 48h. Dosing continued until a threshold was reached where more than one volunteer in a cohort tolerated fewer than 5 doses. Antimicrobial assays were performed with blood samples drawn from the study subjects. In these assays, blood samples were taken from the subjects after they had been dosed with brilacidin. Staphylococcus aureus bacteria was then added to these blood samples, to determine if the brilacidin in the subjects blood would have antimicrobial activity [94] [191] .
Preclinical
Brilacidin demonstrated potent activity against 1000 worldwide strains of Gram-positive staphylococci and streptococci clinical isolates, including those resistant to linezolid, daptomycin and methicillin. These data were presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Disease (ECCMID-2012) in April 2012 [180] .
Brilacidin demonstrated a low incidence for development of resistance in vitro, and high selectivity for bacteria versus mammalian cell types. MIC90 values for brilacidin were 1 µg/mL for S. aureus, 0.5 µg/mL for S. epidermidis, and 1 µg/mL for S. haemolyticus. Brilacidin was bactericidal with a time-kill range between 30 min and 6h. Brilacidin was highly stable in the presence of plasma and isolated hepatocytes from multiple species [186] .
Brilacidin exhibited varying degrees of inhibition against 13 of 19 “priority” fungal pathogens. Brilacidin showed potent stand-alone inhibition in multiple isolates of C. neoformans. Brilacidin showed promising stand-alone inhibition as well in multiple isolates of Mucorales, Fusarium sp., C. glabrata, C. parapsilosis, C. guillermondii, Lomentospora prolificans, Scedosporium apiospermum, Blastomyces dermatitidis and Histoplasma capsulatum. Brilacidin to be synergistic with caspofungin in different types of fungi. Additive effects were similarly observed in Brilacidin combinations with voriconazole and geldanamycin against A. fumigatus, as well as with posaconazole against Mucorales. Separate in vitro laboratory testing evaluating Brilacidin in combination with other conventional antifungals – including caspofungin, fluconazole, posaconazole, amphotericin B and micafungin – demonstrated additive or synergistic inhibition of fungal growth. Brilacidin may favorably modulate the host response to fungal infections [28]
Therapeutic Trials
Top-line data from a phase IIb trial in an intent-to-treat population, demonstrated that three dosing regimens of brilacidin met the primary endpoint of reduction of at least 20% in area of acute bacterial skin and skin structure infections (ABSSSI), compared to baseline, for 48-72 hours, post-first-dosing, without the administration of any rescue antibiotics. The clinical success rate of the three dosing regimens of brilacidin were statistically comparable to that of daptomycin. Brilacidin produced early, high and consistent clinical response in patients with ABSSSI. Clinical response rates at days 2-3, 7-8, 10-14 and 28 were 97.5%, 91.4%, 92.3% and 91.5%; 92.5% 94.3% 97.4% 95.7%; 92.5% 91.4% 97.4% 95.7%; and 87.5% 80.0% 97.4% 93.6%; in the brilacidin low, medium and high dose groups, and the daptomycin group, respectively. The respective 95% confidence intervals around the clinical success rates were 85-100%, 90-100%, 94-100%, and 87-100%. In addition to the intent-to-treat population, similar positive results were obtained in the microbiological intent-to-treat population which consisted of patients who had cultures obtained at the baseline, which were positive for common ABSSSI pathogens. Majority of the cultures grew Staphylococcus aureus, 40% of which included methicillin-resistant Staphylococcus aureus. In this double-blind trial, 215 patients were randomised to one of three dosing regimens of brilacidin (0.4 mg/kg on day 1 then 0.30 mg/kg [low], 0.75 mg/kg on day 1 then 0.35 mg/kg [medium] or 1.0 mg/kg on day 1 then 0.35 mg/kg [high]) once daily for 5 days followed by placebo for 2 days, or daptomycin once daily for 7 days. An approximately 25% of 215 patients were recruited into each treatment arm [189] [78] [179] [181] [76] .
Top line results from a phase II trial demonstrated clear reduction in the incidence of severe stomatitis (OM)(WHO Grade = 3) on treatment with brilacidin 45 mg/15 ml oral rinse as compared with placebo, in patients with head and neck cancer undergoing chemoradiation. Overall reduction was 17.1% (brilacidin: 42.9%; placebo: 60.0%) in modified intent to treat (mITT) population and 23.2% (brilacidin: 36.8%; placebo: 60.0%) in per protocol (PP) population (primary endpoint). The severe OM median duration was 0.0 days for brilacidin in mITT and PP populations (secondary endpoint). Overall Severe OM median durations for placebo were 3.0 days and 5.5 days for the mITT and PP populations. Brilacidin-OM successfully prevented severe oral mucositis from occurring, as well as delayed its onset, in a substantial number of patients compared with placebo, particularly the period from approximately 28-42 days, after the initiation of treatment. Brilacidin-OM appeared to decrease the initial duration of severe oral mucositis (time from the initial WHO Grade = 3 to the first WHO Grade = 2 OM assessment). Initial instance duration median was 33.5% and overall duration median was 35.5% in modified intent to treat (mITT) population. In mITT population, incidences were reduced by 65% in brilacidin group, when compared with placebo (brilacidin: 25.0%; placebo: 71.4%; P = 0.0480) in patients receiving higher concentration of cisplatin (80-100 mg/m2); in per-protocol population, incidences were reduced by 80.3% in brilacidin group, when compared to placebo (brilacidin: 14.3%; placebo: 72.7%; P = 0.0249). The randomised 1:1, parallel, double-blind trial enrolled 61 patients. The oral rinse of brilacidin or placebo was self-administered by patients for three times daily across 7 consecutive weeks in the trial [113] [115] [111] [112] [118] [122] .
Updated results from the first two cohorts from the phase II CTIX-BRI-206 trial demonstrated that a clinically beneficial response was observed in all patients, as measured by the Modified Mayo Disease Activity Index (MMDAI). The primary efficacy endpoint of clinical remission (stool frequency, rectal bleeding, endoscopy sub-scores) was met by three out of six patients from each cohort. Out of the patients from both the cohorts that did not meet the primary endpoint (n=6), all of the patients achieved a partial response (two out of three criteria met). Rate of clinical remission was 60%, 67%, and 75% in the cohort A, B, and C, respectively. Endoscopy subscore of ≤ 1 was achieved by 80%, 67%, and 75% of patients, from the cohort A, B, and C, respectively. Zero rectal bleeding subscore was observed in 80% and 100% of patients of patients from cohort A and cohort B & C, respectively. All patients achieved stool frequency subscore. In Full MMDAI assessment (Stool Frequency + rectal bleeding + endoscopy findings + Physician’s Global Assessment), 100% reduction in 2 patients in Cohort A and 2 patients in Cohort B, 50-75% reduction in 2 patients in Cohort A and 4 patients in Cohort B and 20% reduction in 1 patient in Cohort A was reported. According to partial MMDAI assessment (Stool Frequency + rectal bleeding + endoscopy findings), 100% reduction in 3 patients in Cohort A and 3 patients in Cohort B and 50-83% reduction in 2 patients in Cohort A and 3 patients in Cohort B was observed. All 12 patients reported an improvement in quality of life as measured by the SIBDQ, with, over 40% of patients reporting significant improvements, ranging approximately from 20 points to more than 50 points higher on the 70-point SIBDQ scale. Interim results in four patients treated with brilacidin for ulcerative proctitis demonstrated clinically meaningful improvements, as measured by the Modified Mayo Disease Activity Index (MMDAI). At Day 42, on the Partial MMDAI (accounting for Stool Frequency, Rectal Bleeding, and Physician’s Global Assessment scores), 2 of 4 patients achieved full response (100% reduction) and the other 2 patients had notable improvement (50% reduction). At Day 42, on the MMDAI (equivalent to Partial MMDAI + Endoscopy score; completed by 3 of 4 patients), 1 of 3 patients achieved full response (100% reduction) and 2 of 3 patients had notable improvement (50% reduction). Patient quality of life, as assessed by the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), was improved after 6-weeks of treatment with brilacidin [177] [144] [137] [148] [146] .
COVID-2019 infections
Results from a phase II trial of brilacidin in hospitalised patients with COVID-2019 infections showed that the trial did not meet its primary endpoint in reducing time to sustained recovery through day 29, certain patient subgroups did show treatment benefits of brilacidin for that primary endpoint. For example, patients treated early from onset of symptoms achieved sustained recovery more quickly (brilacidin 5-dose group vs pooled placebo, p=0.03) [25] .
Future Events
| Expected Date | Event Type | Description | Updated |
|---|---|---|---|
| 31 Dec 2022 | Trial Update | Innovation Pharmaceuticals plans a phase III trial for Stomatitis (PO), in 2022 (9324224) | 20 May 2021 |
| 31 Jan 2022 | Trial Update | Innovation Pharmaceuticals plans a phase III trial for Oral mucositis in 2022 [26] | 03 Dec 2021 |
| 31 Dec 2021 | Trial Update | Alfasigma plans a phase II clinical trial for Ulcerative proctitis/Ulcerative proctosigmoiditis (Rectal) in 2021 (9324224) [134] | 20 May 2021 |
| 31 Dec 2021 | Trial Update | Innovation Pharmaceuticals plans a phase II trial for Ulcerative colitis (PO, Capsule) in 2021 (9324224) | 20 May 2021 |
| 05 Feb 2021 | Trial Update | Innovation Pharmaceuticals plans a phase II trial for COVID-2019 infections in February 2021 (IV) [47] | 01 Feb 2021 |
| 31 Dec 2020 | Regulatory Status | Innovation Pharmaceuticals expects IND application approval from the FDA for COVID-2019 infection before Q4 2020 [41] | 22 Dec 2020 |
| 30 Nov 2020 | Regulatory Status | Innovation Pharmaceuticals announces intention to submit an investigational drug (IND) application with the US FDA for COVID-2019 infections in November 2020 [19] | 24 Nov 2020 |
| 30 Sep 2020 | Trial Update | Innovation Pharmaceuticals plans a phase II trial for Ulcerative colitis (PO, Controlled release tablet) in USA by September 2020 (700319549) [174] | 17 Mar 2020 |
| 15 Sep 2020 | Regulatory Status | Innovation Pharmaceuticals plans interactions with the US FDA for COVID-2019 infections in early September 2020 [33] | 06 Oct 2020 |
| 16 Mar 2020 | Trial Update | Regional Biocontainment Labs plans to commence testing of brilacidin for COVID-2019-infections in March 2020 [152] | 03 Apr 2020 |
| 17 Jan 2020 | Trial Update | Innovation Pharmaceuticals and BDD Pharma plan a phase I trial for Ulcerative colitis (In volunteers) in United Kingdom in (PO,Tablet) in January 2020 [132] | 21 Jan 2020 |
| 31 Oct 2018 | Regulatory Status | Innovation Pharmaceuticals plans an end-of-phase II meeting with the FDA in October 2018 [176] | 17 Nov 2018 |
Development History
| Event Date | Update Type | Comment |
|---|---|---|
| 21 Jun 2023 | Patent Information | Innovation Pharmaceuticals has patents pending for Brilacidin in fungal diseases in USA [167] Updated 26 Jun 2023 |
| 21 Jun 2023 | Patent Information | Innovation Pharmaceuticals receives notice of allowance for patent covering arylamide compounds for treatment of viral infections in USA [167] Updated 26 Jun 2023 |
| 06 Jun 2023 | Patent Information | Innovation Pharmaceuticals has patent protection for Brilacidin in the US [167] Updated 26 Jun 2023 |
| 28 Mar 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Inflammatory-bowel-diseases(In volunteers) in United Kingdom (PO, Controlled release) Updated 28 Mar 2023 |
| 15 Mar 2023 | Scientific Update | Antimicrobial data from preclinical studies in COVID-2019 infections released by Innovation Pharmaceuticals [28] Updated 20 Apr 2023 |
| 28 Feb 2023 | Phase Change - No development reported | No recent reports of development identified for phase-I development in Ulcerative-proctitis(In volunteers) in USA (PO, Controlled release) Updated 28 Feb 2023 |
| 28 Feb 2023 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Inflammatory-bowel-diseases in USA (PO, Controlled release) Updated 28 Feb 2023 |
| 13 Dec 2022 | Scientific Update | Pharmacodynamics data from a preclinical study released by Innovation Pharmaceuticals [29] Updated 15 Dec 2022 |
| 04 Oct 2022 | Scientific Update | Pharmacodynamics data from a preclinical study released by Innovation Pharmaceuticals [30] Updated 07 Oct 2022 |
| 28 Aug 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Acne in USA (Topical) Updated 28 Aug 2022 |
| 28 Aug 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Atopic-dermatitis in USA (Topical) Updated 28 Aug 2022 |
| 28 Aug 2022 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Hidradenitis suppurativa in USA (Topical) Updated 28 Aug 2022 |
| 05 Aug 2022 | Trial Update | Innovation Pharmaceuticals and National Institute of Allergy and Infectious Diseases plans a preclinical trial for Monkeypox in USA [102] Updated 13 Aug 2022 |
| 23 Jun 2022 | Scientific Update | Efficacy data from a phase II trial in COVID-19 infections released by Innovation Pharmaceuticals [25] Updated 28 Jun 2022 |
| 23 Jun 2022 | Scientific Update | Pharmacodynamics data from preclinical studies in COVID-2019 infections released by Innovation Pharmaceuticals [25] Updated 28 Jun 2022 |
| 18 Nov 2021 | Regulatory Status | Innovation Pharmaceuticals announces compassionate use of brilacidin for COVID-19 infections [26] Updated 03 Dec 2021 |
| 18 Nov 2021 | Trial Update | Innovation Pharmaceuticals plans a phase III trial for Oral mucositis in 2022 [26] Updated 03 Dec 2021 |
| 25 Oct 2021 | Phase Change - Preclinical | Preclinical trials in Ebola virus infections in USA (unspecified route) [6] Updated 03 Nov 2021 |
| 25 Oct 2021 | Phase Change - Preclinical | Preclinical trials in Marburg virus disease in USA (unspecified route) [6] Updated 03 Nov 2021 |
| 25 Oct 2021 | Phase Change - Preclinical | Preclinical trials in Nipah virus infections in USA (unspecified route) [6] Updated 03 Nov 2021 |
| 25 Oct 2021 | Phase Change - Preclinical | Preclinical trials in West Nile virus infections in USA (unspecified route) [6] Updated 03 Nov 2021 |
| 25 Oct 2021 | Phase Change - Preclinical | Preclinical trials in Zika virus infection in USA (unspecified route) [6] Updated 03 Nov 2021 |
| 13 Aug 2021 | Biomarker Update | Biomarkers information updated Updated 02 Oct 2021 |
| 30 Jul 2021 | Trial Update | Innovation Pharmaceuticals completes a phase II trial in COVID-19 infections in USA and Russia (NCT04784897) Updated 25 Aug 2021 |
| 21 Jul 2021 | Scientific Update | Antiviral data from a preclinical trial in Viral infections presented at the American Society of Virology’s 40th Annual Meeting (ASV-2021) [42] Updated 26 Jul 2021 |
| 03 Jun 2021 | Trial Update | Innovation Pharmaceuticals completes enrolment in its phase II trial for COVID-2019 infections in USA and Russia (IV) [12] (NCT04784897) Updated 08 Jun 2021 |
| 27 May 2021 | Phase Change - Preclinical | Preclinical trials in Alphavirus infections in USA (unspecified route), prior to May 2021 [14] Updated 01 Jun 2021 |
| 27 May 2021 | Phase Change - Preclinical | Preclinical trials in Bunyavirus infections in USA (unspecified route), prior to May 2021 [14] Updated 01 Jun 2021 |
| 20 May 2021 | Trial Update | Innovation Pharmaceuticals plans a phase II trial for Ulcerative colitis (PO, Capsule) in 2021 [21] Updated 20 May 2021 |
| 20 May 2021 | Trial Update | Innovation Pharmaceuticals plans a phase III trial for Stomatitis (PO), in 2022 [21] Updated 20 May 2021 |
| 02 Mar 2021 | Scientific Update | Pharmacodynamics data from a preclinical study in COVID-2019 infections released by Innovation Pharmaceuticals [32] Updated 04 Mar 2021 |
| 22 Feb 2021 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections in Russia (IV) (NCT04784897) Updated 09 Mar 2021 |
| 22 Feb 2021 | Phase Change - II | Phase-II clinical trials in COVID-2019 infections in USA (IV) (NCT04784897) Updated 09 Mar 2021 |
| 29 Jan 2021 | Trial Update | Innovation Pharmaceuticals plans a phase II trial for COVID-2019 infections in February 2021 (IV) [47] Updated 01 Feb 2021 |
| 14 Jan 2021 | Regulatory Status | Brilacidin receives Fast Track designation for COVID-2019 infections [IV] in USA [27] Updated 19 Jan 2021 |
| 21 Dec 2020 | Regulatory Status | US FDA approves IND application to proceed with initiation of a Phase II trial in hospitalized patients COVID-2019 infection [15] Updated 22 Dec 2020 |
| 30 Nov 2020 | Phase Change - Preclinical | Preclinical trials in Coronavirus infections in USA (unspecified route) [48] Updated 02 Dec 2020 |
| 16 Nov 2020 | Regulatory Status | Innovation Pharmaceuticals announces intention to submit an investigational drug (IND) application with the US FDA for COVID-2019 infections in November 2020 [19] Updated 24 Nov 2020 |
| 16 Nov 2020 | Regulatory Status | Innovation Pharmaceuticals submits an overseas clinical trial application with the governing health agency for COVID-2019 infections [19] Updated 24 Nov 2020 |
| 16 Nov 2020 | Trial Update | Innovation Pharmaceuticals plans a phase III trial for Stomatitis (Prevention) (PO) [19] Updated 24 Nov 2020 |
| 02 Oct 2020 | Regulatory Status | Innovation Pharmaceuticals plans to schedule a pre-IND meeting with the US FDA for COVID-2019 infections [18] Updated 06 Oct 2020 |
| 15 Sep 2020 | Scientific Update | Pharmacodynamics data from a preclinical studies in COVID-2019 infections released by Innovation Pharmaceuticals [31] Updated 17 Sep 2020 |
| 24 Aug 2020 | Regulatory Status | Innovation Pharmaceuticals plans interactions with the US FDA for COVID-2019 infections in early September 2020 [33] Updated 06 Oct 2020 |
| 24 Aug 2020 | Scientific Update | Pharmacodynamics data from preclinical studies in COVID-2019 infections released by Innovation Pharmaceuticals [33] [34] Updated 26 Aug 2020 |
| 04 Aug 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections (Prevention) in USA (IV) [37] Updated 07 Aug 2020 |
| 21 Jul 2020 | Scientific Update | Pharmacodynamics data from a preclinical study in COVID-2019 infections released by Innovation Pharmaceuticals [35] Updated 22 Jul 2020 |
| 13 Jul 2020 | Regulatory Status | Innovation Pharmaceuticals expects IND application approval from the FDA for COVID-2019 infection before Q4 2020 [41] Updated 22 Dec 2020 |
| 18 Jun 2020 | Regulatory Status | Innovation Pharmaceuticals intends to seek FDA guidance for a planned trial for COVID-2019 infections in USA [38] Updated 22 Jun 2020 |
| 18 Jun 2020 | Scientific Update | Pharmacodynamics data from a preclinical study in COVID-2019 infections released by Innovation Pharmaceuticals [38] Updated 22 Jun 2020 |
| 26 May 2020 | Scientific Update | Pharmacodynamics data from a preclinical study in COVID-2019 infections released by Innovation Pharmaceuticals [43] Updated 01 Jun 2020 |
| 19 May 2020 | Phase Change - Preclinical | Preclinical trials in COVID-2019 infections in USA (IV) [39] Updated 26 May 2020 |
| 19 May 2020 | Scientific Update | Pharmacodynamics data from preclinical studies in COVID-2019 infections released by Innovation Pharmaceuticals [39] Updated 26 May 2020 |
| 22 Apr 2020 | Licensing Status | Brilacidin is available for licensing as of 20 Apr 2020 for the treatment of COVID-19 infections http://www.ipharminc.com/collaborations [2] Updated 22 Apr 2020 |
| 06 Apr 2020 | Trial Update | Innovation Pharmaceuticals plans a clinical trial for COVID-2019 infections in the US and Europe [44] [39] Updated 14 Apr 2020 |
| 01 Apr 2020 | Scientific Update | Pharmacodynamics data from early research phase in COVID-2019 infections released by Innovation Pharmaceuticals [45] Updated 03 Apr 2020 |
| 17 Mar 2020 | Phase Change | Early research in COVID-2019 infections in USA (IV) [46] Updated 23 Mar 2020 |
| 10 Mar 2020 | Trial Update | Regional Biocontainment Labs plans to commence testing of brilacidin for COVID-2019-infections in March 2020 [152] Updated 03 Apr 2020 |
| 05 Mar 2020 | Trial Update | Innovation Pharmaceuticals plans a phase II trial for Ulcerative colitis (PO, Controlled release tablet) in USA by September 2020 [174] Updated 17 Mar 2020 |
| 24 Feb 2020 | Company Involvement | Innovation Pharmaceuticals submits preliminary summary of brilacidin's potential for COVID-2019-infections to the Biomedical Advanced Research and Development Authority (BARDA) [151] Updated 28 Feb 2020 |
| 13 Feb 2020 | Scientific Update | Top-line adverse events and pharmacokinetics data from the phase I trial in Inflammatory bowel diseases released by Innovation Pharmaceuticals [49] Updated 20 Feb 2020 |
| 12 Feb 2020 | Trial Update | Innovation Pharmaceuticals completes a phase I trial in Inflammatory bowel diseases (In volunteers) in United Kingdom (PO) (NCT04240223) Updated 28 Feb 2020 |
| 06 Feb 2020 | Phase Change - I | Phase-I clinical trials in Inflammatory bowel diseases (In volunteers) in United Kingdom (PO) [49] Updated 20 Feb 2020 |
| 17 Jan 2020 | Phase Change - I | Phase-I clinical trials in Ulcerative proctitis (In volunteers) in USA (PO, Controlled release) [132] [135] Updated 21 Jan 2020 |
| 17 Jan 2020 | Trial Update | Innovation Pharmaceuticals and BDD Pharma plan a phase I trial for Ulcerative colitis (In volunteers) in United Kingdom in (PO,Tablet) in January 2020 [132] Updated 21 Jan 2020 |
| 26 Dec 2019 | Regulatory Status | Medicines and Healthcare products Regulatory Agency approves a Clinical Trial Application for a phase I trial of brilacidin in Ulcerative Colitis in United Kingdom (PO,Tablet) [133] Updated 30 Dec 2019 |
| 10 Dec 2019 | Trial Update | Alfasigma plans a phase II clinical trial for Ulcerative proctitis/Ulcerative proctosigmoiditis (Rectal) in 2021 [21] [134] Updated 20 May 2021 |
| 10 Dec 2019 | Regulatory Status | Innovation Pharmaceuticals submits regulatory documents to the respective health authority for Ulcerative colitis for planned clinical trial [134] Updated 17 Dec 2019 |
| 25 Nov 2019 | Regulatory Status | The US FDA waives Paediatric Investigation Plan for Stomatitis in patients with Head and neck cancer [103] Updated 28 Nov 2019 |
| 13 Nov 2019 | Licensing Status | Brilacidin is available for licensing for Stomatitis (Prevention) as of 13 Nov 2019. www.ipharminc.com Updated 26 Nov 2019 |
| 16 Sep 2019 | Phase Change - Preclinical | Preclinical trials in Ulcerative colitis in United Kingdom (PO, Tablet) before September 2019 [149] Updated 18 Sep 2019 |
| 22 Jul 2019 | Licensing Status | Innovation Pharmaceuticals signs a license agreement with Alfasigma for the development and commercialisation of brilacidin in Ulcerative proctitis/Ulcerative proctosigmoiditis [3] Updated 25 Jul 2019 |
| 30 Jun 2019 | Trial Update | Innovation Pharmaceuticals plans a phase III trial for Stomatitis [100] [41] Updated 06 May 2020 |
| 06 Jun 2019 | Licensing Status | Innovation Pharmaceuticals collaborates with BDD pharma for the developing oral tablets for Inflammatory bowel disease [4] Updated 12 Jun 2019 |
| 19 Feb 2019 | Patent Information | Innovation Pharmaceuticals has patent protection for brilacidin in USA [168] Updated 22 Feb 2019 |
| 14 Jan 2019 | Phase Change - Preclinical | Preclinical trials in Inflammatory bowel diseases in USA (PO) [51] Updated 17 Jan 2019 |
| 14 Jan 2019 | Scientific Update | Pharmacokinetics data from a simulated gastric fluid model in Inflammatory bowel disease released by Innovation Pharmaceuticals [51] Updated 17 Jan 2019 |
| 14 Jan 2019 | Trial Update | Innovation Pharmaceuticals plans a phase III trial in Stomatitis (PO) [51] Updated 17 Jan 2019 |
| 14 Jan 2019 | Trial Update | Innovation Pharmaceuticals plans clinical development in Ulcerative colitis and Crohn's disease (PO) and Ulcerative proctitis (Foam/gel) [51] Updated 17 Jan 2019 |
| 02 Jan 2019 | Patent Information | Innovation Pharmaceuticals receives "issue notification" for a new US patent from the USPTO [169] Updated 07 Jan 2019 |
| 17 Dec 2018 | Regulatory Status | The US FDA completes an End-of-Phase 2 meeting for clinical development programme of brilacidin in Stomatitis (Prevention, in head and neck cancer patients receiving chemoradiation) [104] Updated 21 Dec 2018 |
| 01 Nov 2018 | Patent Information | Innovation Pharmaceuticals has patent protection for brilacidin in USA [170] Updated 09 Nov 2018 |
| 01 Nov 2018 | Patent Information | USPTO issues Notice of Allowance for oral, buccal, and sublingual pharmaceutical compositions of brilacidin [170] Updated 09 Nov 2018 |
| 24 Oct 2018 | Regulatory Status | The US FDA grants an End-of-Phase 2 meeting for clinical development programme of brilacidin in Stomatitis (Prevention, in head and neck cancer patients receiving chemoradiation) [105] Updated 30 Oct 2018 |
| 12 Oct 2018 | Scientific Update | Pharmacodynamics data from preclinical studies released by Innovation Pharmaceuticals [175] Updated 22 Oct 2018 |
| 20 Sep 2018 | Regulatory Status | Innovation Pharmaceuticals plans an end-of-phase II meeting with the FDA in October 2018 [176] Updated 17 Nov 2018 |
| 05 Sep 2018 | Trial Update | Innivation Pharmaceuticals plans a clinical trials for Atopic dermatitis and Acne Updated 07 Sep 2018 |
| 28 Aug 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Diabetic-foot-ulcer in USA Updated 28 Aug 2018 |
| 28 Jun 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Wounds in USA Updated 28 Jun 2018 |
| 09 May 2018 | Scientific Update | Updated efficacy data from a phase II trial in Stomatitis released by Innovation Pharmaceuticals [113] Updated 16 May 2018 |
| 09 May 2018 | Trial Update | Innovation Pharmaceuticals completes a phase II trial in Stomatitis (Prevention) in USA [113] (NCT02324335) Updated 16 May 2018 |
| 28 Feb 2018 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Otitis in USA (Otic) Updated 28 Feb 2018 |
| 08 Jan 2018 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Intestinal infections in USA (PO) (Innovation pipeline, January 2018) Updated 08 Jan 2018 |
| 08 Jan 2018 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Ophthalmic infections in USA (Ophthalmic) (Innovation pipeline, January 2018) Updated 08 Jan 2018 |
| 08 Jan 2018 | Phase Change - Discontinued(Preclinical) | Discontinued - Preclinical for Ulcerative colitis in USA (Topical) (Innovation pipeline, January 2018) Updated 08 Jan 2018 |
| 03 Jan 2018 | Scientific Update | Updated efficacy data from a phase II trial in Stomatitis (Prevention) released by Innovation Pharmaceuticals [112] Updated 08 Jan 2018 |
| 28 Dec 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Ophthalmic-infections in USA (Ophthalmic) Updated 28 Dec 2017 |
| 12 Dec 2017 | Patent Information | Innovation Pharmaceuticals has patent protection for Brilacidin in Europe, Japan, Taiwan, China, Australia and South Africa [171] Updated 15 Dec 2017 |
| 12 Dec 2017 | Patent Information | Innovation Pharmaceuticals has patents pending for Brilacidin in Russia and South Korea [171] Updated 15 Dec 2017 |
| 11 Dec 2017 | Scientific Update | Top line efficacy and adverse events data from a phase II trial in Stomatitis (Prevention) released by Innovation Pharmaceuticals [115] Updated 15 Dec 2017 |
| 22 Nov 2017 | Trial Update | Innovation Pharmaceuticals completes a phase II trial in Stomatitis (Prevention) in USA (Topical) [109] Updated 01 Nov 2017 |
| 16 Nov 2017 | Regulatory Status | Innovation Pharmaceuticals plans to follow expedited approval procedure for Stomatitis in Europe [108] Updated 22 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Intestinal-infections in USA (PO) Updated 04 Nov 2017 |
| 04 Nov 2017 | Phase Change - No development reported | No recent reports of development identified for preclinical development in Ulcerative-colitis in USA (Topical) Updated 04 Nov 2017 |
| 26 Oct 2017 | Regulatory Status | Innovation Pharmaceuticals plans to apply for FDA Breakthrough Therapy Designation for Stomatitis [109] Updated 01 Nov 2017 |
| 26 Oct 2017 | Trial Update | Innovation Pharmaceuticals plans a pivotal phase III trial in Stomatitis [109] Updated 01 Nov 2017 |
| 07 Aug 2017 | Trial Update | Cellceutix plans a clinical trial for Atopic dermatitis [116] Updated 08 Aug 2017 |
| 07 Aug 2017 | Trial Update | Innovation Pharmaceuticals completes enrolment in its phase II trial for Stomatitis (Prevention) in USA [116] Updated 08 Aug 2017 |
| 13 Jul 2017 | Scientific Update | Additional efficacy data from a phase II trial in Ulcerative colitis released by Innovation Pharmaceuticals [177] Updated 19 Jul 2017 |
| 26 Jun 2017 | Trial Update | Innovation pharmaceuticals completes a phase II trial in Ulcerative colitis in USA [136] Updated 04 Jul 2017 |
| 07 Jun 2017 | Company Involvement | Cellceutix is now called Innovation Pharmaceuticals Updated 09 Jun 2017 |
| 18 May 2017 | Trial Update | Cellceutix Corporation completes enrolment in its phase II trial for Ulcerative colitis [147] Updated 25 May 2017 |
| 27 Mar 2017 | Scientific Update | Preliminary interim efficacy, pharmacokinetics and adverse events data from a phase II trial in Stomatits released by Cellceutix [118] Updated 04 Apr 2017 |
| 08 Mar 2017 | Scientific Update | Interim efficacy, pharmacokinetics and adverse events data from a phase II proof-of-concept trial in Ulcerative colitis released by Cellceutix [148] Updated 19 Mar 2017 |
| 17 Jan 2017 | Trial Update | Cellceutix completes enrolment in the second cohort in its phase II trial for Ulcerative colitis in USA (Rectal) [140] Updated 23 Jan 2017 |
| 07 Dec 2016 | Scientific Update | Interim adverse events data from a phase II proof-of-concept trial in Ulcerative colitis released by Cellceutix [141] Updated 13 Dec 2016 |
| 07 Dec 2016 | Trial Update | Cellceutix plans clinical trials for hidradenitis suppurativa [141] Updated 13 Dec 2016 |
| 07 Dec 2016 | Trial Update | Cellceutix plans gastroenterological studies for foam and tablet formulations of brilacidin (Cellceutix website) Updated 13 Dec 2016 |
| 01 Nov 2016 | Phase Change - Preclinical | Preclinical trials in Atopic dermatitis in USA (Topical) (Cellceutix website, November 2016) [155] Updated 13 Dec 2016 |
| 01 Nov 2016 | Phase Change - Preclinical | Preclinical trials in Hidradenitis suppurativa in USA (Topical) (Cellceutix website, November 2016) [155] Updated 13 Dec 2016 |
| 26 Oct 2016 | Phase Change - Preclinical | Preclinical trials in Acne in USA (Topical) [154] [155] Updated 13 Dec 2016 |
| 26 Oct 2016 | Trial Update | Cellceutix plans clinical trials for Acne [154] Updated 28 Oct 2016 |
| 10 Oct 2016 | Scientific Update | Interim pharmacokinetics and efficacy data from a phase II trial in Ulcerative colitis released by Cellceutix [144] Updated 14 Oct 2016 |
| 15 Jun 2016 | Phase Change - II | Phase-II clinical trials in Ulcerative proctitis in USA (Rectal) [11] [178] Updated 22 Jun 2016 |
| 26 Feb 2016 | Regulatory Status | Cellceutix submits Special Protocol Assessment (SPA) to the US FDA for its planned phase III clinical trial Updated 02 Mar 2016 |
| 09 Feb 2016 | Regulatory Status | Cellceutix announces intention to submit Special Protocol Assessment (SPA) to the US FDA for its planned phase III clinical trial [54] Updated 11 Feb 2016 |
| 25 Nov 2015 | Regulatory Status | Brilacidin receives Fast Track designation for Stomatitis [Topical,Liquid] (Prevention) in USA [110] Updated 29 Nov 2015 |
| 15 Sep 2015 | Regulatory Status | Cellceutix submits Paediatric Study Plan (PSP) to the US FDA for Skin and soft tissue infections [56] Updated 15 Oct 2015 |
| 31 Aug 2015 | Active Status Review | Brilacidin is still in phase-II development for Skin and soft tissue infections in Canada, Russia, Ukraine and USA Updated 31 Aug 2015 |
| 20 Jul 2015 | Regulatory Status | The US FDA recommends advancing the brilacidin programme to phase III development [57] Updated 22 Jul 2015 |
| 01 Jun 2015 | Phase Change | Early research in Hidradenitis suppurativa in USA (unspecified route) Updated 06 Jul 2015 |
| 21 Apr 2015 | Trial Update | Cellceutix plans a phase II trial for Ulcerative colitis in Europe (Topical) [60] Updated 27 May 2015 |
| 21 Apr 2015 | Trial Update | Cellceutix plans a phase III trial for Skin and soft tissue infections in USA [60] Updated 26 May 2015 |
| 08 Dec 2014 | Trial Update | Cellceutix plans to initiate a phase II trial in Stomatitis in USA Updated 14 Mar 2015 |
| 08 Dec 2014 | Regulatory Status | Brilacidin receives Qualified Infectious Disease Product (QIDP) designation from the FDA for Acute bacterial skin and skin structure infections [99] Updated 09 Dec 2014 |
| 24 Nov 2014 | Licensing Status | Cellceutix enters into an agreement with a division of one of the largest US pharmaceutical companies to test brilacidin for the prevention of infection in certain implanted devices [7] Updated 03 Dec 2014 |
| 11 Nov 2014 | Licensing Status | Brilacidin is available for licensing in World as of 11 Nov 2014. http://cellceutix.com/ Updated 13 Nov 2014 |
| 23 Oct 2014 | Scientific Update | Top-line efficacy and adverse events data from a phase IIb trial in Skin and soft tissue infections released by Cellceutix [62] Updated 14 Nov 2014 |
| 13 Oct 2014 | Regulatory Status | US FDA approves IND application for phase II trial of brilacidin in Stomatitis [64] Updated 15 Oct 2014 |
| 09 Sep 2014 | Regulatory Status | Cellceutix files an IND application with the US FDA for Stomatitis [65] Updated 12 Sep 2014 |
| 31 Aug 2014 | Trial Update | Cellceutix completes a phase IIb trial in Skin and soft tissue infections in USA [63] (NCT02052388) Updated 30 Oct 2014 |
| 19 Aug 2014 | Trial Update | Cellceutix completes enrolment in a phase IIb trial for Skin and soft tissue infections in USA (NCT02052388) Updated 21 Aug 2014 |
| 14 Aug 2014 | Phase Change - II | Phase-II clinical trials in Stomatitis (Prevention) in USA (Topical) (NCT02324335) Updated 27 May 2015 |
| 14 Jul 2014 | Phase Change - Preclinical | Preclinical trials in Diabetic foot ulcer in USA (unspecified route) Updated 14 Aug 2014 |
| 19 May 2014 | Scientific Update | Pharmacodynamics data from a preclinical study in Wounds (non-infected) released by Cellceutix [158] Updated 26 May 2014 |
| 01 May 2014 | Phase Change - Preclinical | Preclinical trials in Wounds in USA (unspecified route) Updated 26 May 2014 |
| 24 Feb 2014 | Scientific Update | Pharmacodynamics data from a preclinical trial in Otitis media released by Cellceutix [8] Updated 25 Feb 2014 |
| 18 Feb 2014 | Phase Change - II | Phase-II clinical trials in Skin and soft tissue infections in USA (IV) Updated 19 Feb 2014 |
| 01 Jan 2014 | Phase Change - Preclinical | Preclinical trials in Otitis in USA (Otic) Updated 24 Jan 2014 |
| 20 Dec 2013 | Regulatory Status | Cellceutix applies for orphan drug status for briliacidin for oral mucositis in USA [130] Updated 24 Dec 2013 |
| 04 Nov 2013 | Phase Change - Preclinical | Preclinical trials in Ophthalmic infections in USA (Ophthalmic) Updated 06 Nov 2013 |
| 16 Sep 2013 | Phase Change - Preclinical | Preclinical trials in Ulcerative colitis in USA (Topical) Updated 04 Dec 2014 |
| 16 Sep 2013 | Phase Change - Preclinical | Preclinical trials in Intestinal infections in USA (PO) Updated 06 Nov 2013 |
| 04 Sep 2013 | Licensing Status | Cellceutix acquires brilacidin from PolyMedix [9] Updated 11 Sep 2013 |
| 01 Apr 2013 | Company Involvement | PolyMedix files for Chapter 7 bankruptcy [9] Updated 11 Sep 2013 |
| 20 Sep 2012 | Company Involvement | PolyMedix receives a Phase I grant from the National Cancer Institute for preclinical development of brilacidin in Stomatitis [129] Updated 24 Sep 2012 |
| 12 Sep 2012 | Scientific Update | Pharmacokinetics data from a preclinical study & a phase I trial in Healthy volunteers presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2012) [85] Updated 10 Oct 2012 |
| 11 Sep 2012 | Scientific Update | Final efficacy and adverse event data from a phase II trial in acute bacterial Skin and soft tissue infections released by PolyMedix [78] Updated 14 Sep 2012 |
| 04 Jun 2012 | Scientific Update | Pharmacodynamics data from preclinical studies in Stomatitis presented at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO-2012) [128] Updated 05 Jun 2012 |
| 23 Apr 2012 | Scientific Update | Final efficacy and adverse events data from a phase II trial in Skin and soft tissue infections released by PolyMedix [179] Updated 24 Apr 2012 |
| 02 Apr 2012 | Scientific Update | Antimicrobial data from preclinical trials in Bacterial infections presented at the 21st Annual European Congress of Clinical Microbiology and Infectious Disease (ECCMID-2012) [180] Updated 04 Apr 2012 |
| 01 Mar 2012 | Trial Update | PolyMedix completes its phase II trial for Skin and soft tissue infections in Canada, Russia and Ukraine (NCT01211470) Updated 11 Sep 2013 |
| 04 Jan 2012 | Trial Update | PolyMedix completes enrolment in its phase II trial for Skin and soft tissue infections in Canada, Russia and Ukraine (NCT01211470) Updated 06 Jan 2012 |
| 07 Dec 2011 | Scientific Update | Interim efficacy and adverse events data from a phase II trial in Skin and soft tissue infections released by PolyMedix [181] Updated 08 Dec 2011 |
| 20 Sep 2011 | Scientific Update | Pharmacokinetics & adverse events data from a phase I trial in Healthy volunteers presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2011) [84] Updated 27 Sep 2011 |
| 12 Sep 2011 | Phase Change - II | Phase-II clinical trials in Skin and soft tissue infections in Russia (IV) Updated 14 Sep 2011 |
| 12 Sep 2011 | Phase Change - II | Phase-II clinical trials in Skin and soft tissue infections in Ukraine (IV) Updated 14 Sep 2011 |
| 19 May 2011 | Phase Change - Preclinical | Preclinical trials in Stomatitis in USA (Topical) Updated 23 May 2011 |
| 10 May 2011 | Scientific Update | Pharmacokinetics, antimicrobial & adverse events data from two phase I trials in Healthy volunteers presented at the 21st European Congress of Clinical Microbiology and Infectious Diseases and the 27th International Congress of Chemotherapy (ECCMID-ICC-2011) [182] , [87] Updated 17 Jun 2011 |
| 28 Apr 2011 | Scientific Update | Pharmacodynamics data from a preclinical study in Bacterial infections released by PolyMedix [183] Updated 29 Apr 2011 |
| 25 Feb 2011 | Scientific Update | Final adverse events data from a Phase I trial in Healthy volunteers released by PolyMedix [86] Updated 28 Feb 2011 |
| 25 Feb 2011 | Trial Update | PolyMedix completes a phase I dose-escalation trial in Healthy volunteers in USA [86] Updated 28 Feb 2011 |
| 11 Nov 2010 | Phase Change - I | Phase-I clinical trials in Bacterial infections (in volunteers) in USA (IV) Updated 15 Nov 2010 |
| 11 Nov 2010 | Regulatory Status | US FDA approves IND application for brilacidin in Bacterial infections [88] Updated 15 Nov 2010 |
| 29 Sep 2010 | Phase Change - II | Phase-II clinical trials in Skin and soft tissue infections in Canada (IV) Updated 29 Sep 2010 |
| 31 Mar 2010 | Trial Update | PolyMedix completes phase I trials in Bacterial infections Updated 13 Jul 2010 |
| 31 Mar 2010 | Scientific Update | Final adverse events and antimicrobial data from a phase Ib trial in Staphylococcal infections released by PolyMedix [91] Updated 01 Apr 2010 |
| 12 Mar 2010 | Phase Change - Suspended(Preclinical) | Suspended - Preclinical for Intestinal infections in USA (PO) Updated 09 Nov 2010 |
| 12 Mar 2010 | Phase Change - Suspended(Preclinical) | Suspended - Preclinical for Ophthalmic infections in USA (Topical) Updated 09 Nov 2010 |
| 12 Mar 2010 | Scientific Update | Interim safety and antimicrobial data from a phase I trial in Bacterial infections released by PolyMedix [93] Updated 15 Mar 2010 |
| 19 Dec 2009 | Scientific Update | Adverse events and antimicrobial data from a phase I trial in Bacterial infections released by PolyMedix [94] Updated 22 Dec 2009 |
| 15 Sep 2009 | Scientific Update | Pharmacodynamics and pharmacokinetic data from a preclinical trial in Bacterial infections presented at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC-2009) [184] , [185] Updated 07 Oct 2009 |
| 06 Jun 2009 | Trial Update | PolyMedix initiates patient dosing in a phase I trial in healthy volunteers in USA Updated 09 Jun 2009 |
| 26 May 2009 | Trial Update | PolyMedix receives regulatory clearance from Health Canada to commence a second phase I clinical trial of brilacidin in healthy volunteers Updated 26 May 2009 |
| 11 Dec 2008 | Scientific Update | Adverse events and pharmacokinetics data from a phase I trial in Healthy volunteers released by PolyMedix [97] Updated 12 Dec 2008 |
| 28 Oct 2008 | Scientific Update | Antimicrobial, adverse events, and pharmacodynamics data from preclinical trials in Bacterial infections presented at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Annual Meeting of the Infectious Diseases Society of America (ICAAC/IDSA-2008) [186] , [187] Updated 10 Nov 2008 |
| 22 Aug 2008 | Phase Change - I | Phase-I clinical trials in Bacterial infections in Canada (IV) Updated 25 Aug 2008 |
References
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Cellceutix Announces Company Name Change to Innovation Pharmaceuticals Inc.
Media Release -
Screening of 11,552 Compounds Identifies Innovation Pharmaceuticals Brilacidin as One of the Most Promising Potential Inhibitors of the Novel Coronavirus COVID-19.
Media Release -
Innovation Pharmaceuticals Announces License Agreement with Alfasigma S.p.A. for the Development and Commercialization of Brilacidin in Ulcerative Proctitis/Ulcerative Proctosigmoiditis.
Media Release -
Innovation Pharmaceuticals Signs Agreement for Advanced Oral Tablet Technology in Treating Inflammatory Bowel Disease.
Media Release -
Innovation Pharmaceuticals Signs Drug Product Manufacturing Contract with CoreRx to Formulate and Package Brilacidin for Oral Mucositis in Sachet Form.
Media Release -
Innovation Pharmaceuticals' COVID-19 Clinical Trial Topline Results Anticipated to Be Reported the Week of November 8th.
Media Release -
Cellceutix: December to Be Momentous Month in Company's History.
Media Release -
Cellceutix Selects Dr. Reddy's Laboratories for Formulation of Brilacidin for Ophthalmic and Otitis Infections.
Media Release -
Cellceutix Acquires PolyMedix Assets From Bankruptcy Court, Gains Ownership of Two Clinical Stage Drugs, Multiple Compounds, and Equipment Assets.
Media Release -
Cellceutix Announces Breakthrough in the Formulation of Its Novel Antibiotic Brilacidin(Tm), Plans Studies to Treat Diabetic Foot Ulcers.
Media Release -
Cellceutix Starts Phase 2 Trial of Brilacidin as a Novel Therapy for Ulcerative Proctitis.
Media Release -
Last Patient Last Visit Completed in Innovation Pharmaceuticals Phase 2 Clinical Trial of Brilacidin for COVID-19; Trial Database Undergoing Review in Preparation for Database Lock.
Media Release -
Innovation Pharma Completes Interim Safety Data ReviewDMC Approves Increased Dosing Frequency in Phase 2 Clinical Trial of Brilacidin in Hospitalized COVID-19 Patients.
Media Release -
Patient Enrollment Reaches 90 Percent in Innovation Pharmaceuticals Phase 2 Clinical Trial of Brilacidin for COVID-19.
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FDA Grants IND Approval for Phase 2 Clinical Trial of Innovation Pharmaceuticals Brilacidin for Treating COVID-19.
Media Release -
Innovation Pharma Provides Study Details for Ongoing Phase 2 Clinical Trial of Brilacidin in Hospitalized COVID-19 Patients.
Media Release -
Innovation Pharmaceuticals Receives Pre-IND Response from FDA on COVID-19 Trial.
Media Release -
Innovation Pharmaceuticals Announces Pre-IND Meeting Request Granted by FDA for the Study of Brilacidin for the Treatment of COVID-19.
Media Release -
Innovation Pharmaceuticals Announces Overseas Regulatory Filing Submitted For COVID-19 Clinical Study.
Media Release -
Innovation Pharma Announces Brilacidin Abstract Accepted for Oral Presentation at the American Society for Virology's Annual Meeting.
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Innovation Pharma Files Form 10-Q; Patient Enrollment in Phase 2 Clinical Trial of Brilacidin for COVID-19 Tops 70 Percent.
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Immutep To Announce New TACTI-002 and INSIGHT-004 Data in Poster Presentations and Discussion at the ASCO 2021 Annual Meeting.
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Recruitment and Enrollment Underway at Eight Sites for Innovation Pharmas Phase 2 Clinical Trial of Brilacidin for COVID-19.
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A Phase 2, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Brilacidin in Hospitalized Participants With COVID-19
ctiprofile -
Innovation Pharmaceuticals Reports Brilacidin Inhibits Omicron, Delta, Gamma and Alpha SARS-CoV-2 Variants Based on In Vitro Testing by NIH/NIAID-Sponsored and Rutgers University Researchers.
Media Release -
Innovation Pharmaceuticals Provides Brilacidin Program Update.
Media Release -
Innovation Pharmaceuticals Brilacidin for the Treatment of COVID-19 Receives FDA Fast Track Designation.
Media Release -
Innovation Pharmaceuticals Announces New Antifungal Testing of Brilacidin by NIH/NIAID-Affiliated and Other Academic Researchers.
Media Release -
Innovation Pharmaceuticals Reports New In Vivo Antifungal Data Showing Brilacidins Potential for Treating Fungal Keratitis.
Media Release -
Innovation Pharmaceuticals Announces Publication of Scientific Article on the Antifungal Activity of Brilacidin.
Media Release -
Laboratory Testing of Brilacidin for COVID-19 in Combination with Remdesivir Reduces Viral Load by Nearly 100 Percent.
Media Release -
Innovation Pharmaceuticals Announces Publication of Peer-Reviewed Scientific Article in the Journal Viruses on the Anti-SARS-CoV-2 Properties of Brilacidin.
Media Release -
COVID-19 Drug Candidate Brilacidin Achieves a Selectivity Index Among the Highest Reported, Exhibiting Potent Anti-SARS-CoV-2 Activity at Low Concentrations; Clinical Trial Forthcoming.
Media Release -
Innovation Pharmaceuticals and George Mason University Announce Public Release of Laboratory Testing Results Demonstrating Brilacidins COVID-19 Treatment Potential.
Media Release -
Innovation Pharmaceuticals Brilacidin Inhibits Novel Coronavirus (COVID-19) by Almost 90% at the Lowest Concentration Tested to Date in a Human Lung Cell Line.
Media Release -
Innovation Pharmaceuticals Provides Update on Brilacidin Antiviral Research.
Media Release -
Innovation Pharmaceuticals and U.S. Regional Biocontainment Laboratory Nearing Completion of Brilacidin Anti-SARS-CoV-2 (COVID-19) In Vitro Testing.
Media Release -
Innovation Pharmaceuticals Brilacidin Inhibits SARS-CoV-2 (COVID-19) by 97 Percent in a Human Lung Cell Line.
Media Release -
Innovation Pharmaceuticals Brilacidin Reduces Viral Titer of SARS-CoV-2 (COVID-19) by 75 percent After Only 1 Hour of Preincubation in In Vitro Study at BSL-3 Facility; Demonstrates Potent and Rapid Virucidal Activity.
Media Release -
In Vitro Testing of Innovation Pharmaceuticals Brilacidin for COVID-19 Shows Consistent Anti-SARS-CoV-2 Efficacy; Manufacturing Preparation Underway for COVID-19 Clinical Trial.
Media Release -
Innovation Pharmaceuticals Clinical Trial Testing of Brilacidin Against SARS-CoV-2 (COVID-19) Targeted to Commence Q4 2020.
Media Release -
Innovation Pharmaceuticals Announces New In Vitro Data Supporting Brilacidins Broad-Spectrum Antiviral Potential Presented at the American Society of Virologys Annual Meeting.
Media Release -
Innovation Pharmaceuticals Receives Data from Public Health Research Institute Showing Brilacidin Inhibits SARS-CoV-2 (COVID-19) in a Human Cell Line.
Media Release -
Brilacidin-MOA. Internet-Doc 2020;.
Available from: URL: https://static1.squarespace.com/static/5715352e20c647639137f992/t/5e9cebd48660e44c2754fa00/1587342453349/Brilacidin+for+COVID-19+Overview+-+MOA%2C+PreClinical+Data%2C+Academic+Literature+-+4.20.20.pdf -
Innovation Pharmaceuticals Receives Data Supporting Brilacidins Direct Inhibition of SARS-CoV-2, the Novel Coronavirus Responsible for COVID-19.
Media Release -
Innovation Pharmaceuticals Brilacidin to be Researched as Possible Novel Coronavirus (COVID-19) Vaccine; Brilacidin Now Being Tested as Drug and Vaccine at Different Institutions.
Media Release -
Innovation Pharmaceuticals' Phase 2 Clinical Trial of Brilacidin for Treating COVID-19 Scheduled to Begin Next Week.
Media Release -
Innovation Pharmaceuticals COVID-19 Clinical Trial to Support Additional Development of Brilacidin as a Pan-Coronavirus Therapeutic.
Media Release -
Innovation Pharmaceuticals Phase 1 Trial of Brilacidin for Ulcerative Colitis Meets Primary Endpoints; Positive Topline Results of Oral Brilacidin.
Media Release -
A Phase 1, Single Dose Escalation Study to Investigate the Use of Delayed Release Tablets for Colonic Delivery of Brilacidin in Healthy Volunteers
ctiprofile -
Innovation Pharmaceuticals Completes Gastric Fluid Testing of Brilacidin Supporting Development of an Oral Dosage Form to Treat Inflammatory Bowel Disease.
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Cellceutix Corporation Provides Business Update and Timeline of Upcoming Milestones.
Media Release -
Cellceutix First Annual Shareholder Meeting December 15, 2015.
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Cellceutix to submit special protocol assessment request to FDA for phase III clinical Study of antibiotic.
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Cellceutix Completes Lab Testing of Brilacidin for Planned Phase 3 Trial for Acute Bacterial Skin and Skin Structure Infections.
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Cellceutix Provides Update on Its Phase 3 Preparations for ABSSSI.
Media Release -
Cellceutix to Start Brilacidin Phase 3 Program in ABSSSI.
Media Release -
A Phase 3, Multicenter, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Single-Dose IV Brilacidin versus IV Vancomycin Followed by Optional PO Linezolid for the Treatment of Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)
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A second phase III trial of brilacidin for the treatment of acute bacterial skin and skin structure infections
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Cellceutix Provides Corporate Update.
Media Release -
Cellceutix Reports Positive Results of Brilacidin in Microbiological Intent-to-Treat Population in Phase 2b ABSSSI Trial; Additional Pharmacokinetic Information to Be Submitted.
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Cellceutix Announces Positive Top-Line Data From Phase 2b ABSSSI Trial; Single-Dose Brilacidin Comparable to 7-Days of Daptomycin.
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Cellceutix Provides Update to Shareholders.
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Cellceutix Investigational New Drug (IND) Application Becomes Effective, Selects First Site for Phase 2 Clinical Trial of New Treatment for Oral Mucositis.
Media Release -
Cellceutix Provides Initial Observations of Completed ABSSSI Phase 2b Trial; Company Submits Investigational New Drug Application to FDA for Phase 2 Trial of Brilacidin-OM for Oral Mucositis.
Media Release -
Cellceutix Brilacidin ABSSSI Trial Gets Positive Review by Data Safety Monitoring Board; Best Possible Outcome, No Treatment-Related Serious Adverse Events (SAEs).
Media Release -
Cellceutix Enrolls First Patients in Phase 2b ABSSSI Clinical Trial.
Media Release -
Cellceutix Plans Phase 2b Trial of New Antibiotic, Reports Fifth Cohort Complete in Novel Cancer Drug Clinical Trial.
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Cellceutix Submits Investigational New Drug Application (IND) for Clinical Trial of New Anti-Psoriasis Drug, Enrollment Underway in Phase 2b Clinical Trials of Brilacidin.
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Cellceutix Confident in Its Formidable Antibiotic Arsenal.
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Cellceutix Reports 20 Percent Enrollment Completed in Phase 2b Trial of Brilacidin as Short-Course Therapy for ABSSSI.
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Cellceutix Expands to Gram-Negative Bacterial Infections.
Media Release -
Cellceutix Reports 14 Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Patients Treated in Phase 2b Clinical Trial.
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Cellceutix Completes Enrollment in Phase 2b Clinical Trial of Brilacidin for Acute Bacterial Skin and Skin Structure Infections (ABSSSI).
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PolyMedix Announces Successful Meeting With FDA for Brilacidin.
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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)
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Cellceutix Announces Brilacidin Data to Be Presented by ICPD at the Joint 55th Interscience Conference on Antimicrobial Agents & Chemotherapy (ICAAC).
Media Release -
PolyMedix Presents New Data on Its Defensin-Mimetic Antibiotics at 52nd Annual ICAAC
Media Release -
PolyMedix Completes Enrollment in Phase 2 Trial With PMX-30063 Defensin-Mimetic Antibiotic.
Media Release -
PolyMedix Provides Updates on Lead Clinical Programs.
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PolyMedix Initiates Phase 2 Clinical Trial with Novel Antibiotic, PMX-30063.
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Randomized, Dose Ranging, Active Controlled Efficacy and Safety Evaluation of PMX-30063 As Initial Treatment for Acute Bacterial Skin and Skin Structure Infections (ABSSSI) Caused by Staphylococcus Aureus
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Multiple dose study of brilacidin [PMX 30063] in male and female volunteers in the USA
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PolyMedix Successfully Completes Phase 1 Exposure Escalation Safety Study With PMX-30063 Antibiotic.
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Korczak B, Echols R, Walters E. PMX30063 - understanding neuronal effects in multi dose-phase 1 clinical study. 21st-ECCMID-27th-ICC-2011 2011; abstr. N/A.
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PolyMedix Obtains Regulatory Clearance for its United States IND Application for PMX-30063 Antibiotic.
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Phase Ib multiple-dose trial of brilacidin [PMX 30063] in volunteers.
ctiprofile -
Webcast Alert: PMX-30063 Phase 1B Clinical Study Results.
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PolyMedix Successfully Completes Phase 1B Clinical Study With Novel Antibiotic PMX-30063.
Media Release -
PolyMedix Announces Planned Milestones for 2010.
Media Release -
PolyMedix Presents PMX-30063 Antibiotic Data at 8th World Congress on Trauma, Shock, Inflammation and Sepsis-TSIS 2010.
Media Release -
PolyMedix successfully completes main portions of phase 1B clinical study with PMX-30063 novel antibiotic drug candidate.
Media Release -
PolyMedix Initiates Dosing in Second Phase I Clinical Study of Novel Systemic Antibiotic Compound.
Media Release -
Phase Ia trial of brilacidin [PMX 30063] in volunteers.
ctiprofile -
PolyMedix Announces Positive Phase I Clinical Data with PMX-30063 Novel Antibiotic Drug Candidate.
Media Release -
PolyMedix Receives Regulatory Clearance to Initiate Phase I Clinical Study of Novel Systemic Antibiotic Compound.
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Cellceutix Antibiotic Brilacidin Receives QIDP Designation From FDA.
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Innovation pharmaceuticals, Form 10-K. Internet-Doc 2020;.
Available from: URL: https://www.sec.gov/Archives/edgar/data/1355250/000147793219005611/ipix_10k.htm -
Cellceutix Completes Acquisition of PolyMedix Assets, Immediately Plans Brilacidin(Tm) Phase 2b Clinical Trial for Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Phase 2 Clinical Trial for Oral Mucositis.
Media Release -
Innovation Pharmaceuticals Announces NIH/NIAID-Affiliated Researchers to Evaluate Brilacidin's Treatment Potential Against Monkeypox.
Media Release -
Innovation Pharmaceuticals and FDA Agree to Waive Initial Pediatric Study Plan Requirement Regarding Brilacidin for the Prevention of Oral Mucositis.
Media Release -
Innovation Pharmaceuticals Completes End-of-Phase 2 Meeting with FDA; Brilacidin Oral Rinse to Advance Into Phase 3 Clinical Trials for Prevention of Severe Oral Mucositis.
Media Release -
Innovation Pharmaceuticals Granted End-of-Phase 2 Meeting.
Media Release -
Innovation Pharmaceuticals European Subsidiary, IPIX Pharma Ltd., Granted Meeting with European Medicines Agency (EMA) to Discuss International Phase 3 Brilacidin Oral Mucositis Program.
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Innovation Pharmaceuticals Requesting European Medicines Agency (EMA) Input for International Phase 3 Brilacidin Oral Mucositis Program.
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Innovation Pharmaceuticals Offers Perspectives on Brilacidin as a Potential Preventative Treatment for Oral Mucositis in Head and Neck Cancer Patients.
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Innovation Pharmaceuticals Aims to Develop First Drug for Approval in Prevention of Oral Mucositis in Head and Neck Cancer Patients as Phase 2 Clinical Trial of Brilacidin Completes.
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FDA Grants Fast Track Designation to Cellceutix's Brilacidin-OM for Oral Mucositis.
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Innovation Pharmaceuticals Data from Phase 2 Brilacidin Oral Mucositis (OM) Trial in Head and Neck Cancer Show Notable Reductions in Median Duration of Severe OM and in Number of Unplanned Visits/Hospital Admissions Due to OM.
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Innovation Pharmaceuticals Brilacidin Meets Key Secondary Endpoint in Phase 2 Trial, Delays Onset of Severe Oral Mucositis (SOM); Latest Results Further Support Topline Data Showing Trial Met Primary Endpoint of Reducing Incidence of SOM.
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Innovation Pharmaceuticals Concludes Data Analysis of its Phase 2 Clinical Trial for Severe Oral Mucositis in Head and Neck Cancer; Positioning to Fill a Substantial Void in Supportive Cancer Care.
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Innovation Pharmaceuticals Signs Drug Supply Contract with Evonik to Bulk Produce Commercial-Grade Brilacidin.
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Innovation Pharmaceuticals Reports Positive Topline Results from Phase 2 Placebo-Controlled Trial of Brilacidin for the Prevention of Oral Mucositis in Head and Neck Cancer Patients; Company Targets a Therapeutic Leadership Position in Global OM Market.
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Innovation Pharmaceuticals Completes Patient Enrollment in Phase 2 Study of Brilacidin for the Prevention of Severe Oral Mucositis.
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Final Patient Completes Treatment in Innovation Pharmaceuticals Phase 2 Trial of Brilacidin for Preventing Oral Mucositis in Cancer Patients.
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Cellceutix Reports Very Encouraging Interim Analysis of Phase 2 Drug Candidate Brilacidin for Severe Oral Mucositis (OM) in Head and Neck Cancer Patients; High Potential for Preventative Treatment.
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Enrollment in Cellceutix Phase 2 Clinical Trial of Brilacidin-OM For Oral Mucositis Expanding to Additional Centers.
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Enrollment Begins in Cellceutix Phase 2 Trial of Brilacidin-OM to Prevent Oral Mucositis in Patients Undergoing Chemoradiation.
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Cellceutix Reports Results for Quarter Ended March 31, 2015; Enrollment for Oral Mucositis Studies to Begin This Month.
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Phase 2 Study to Evaluate the Efficacy & Safety of Brilacidin Oral Rinse Administered Daily for 7 Weeks in Attenuating Oral Mucositis in Patients With Head & Neck Cancer Receiving Chemoradiation
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Cellceutix Prepares for Phase 2 Clinical Trial of Brilacidin-OM for Oral Mucositis.
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Patient Enrollment in Cellceutix Phase 2 Clinical Trial of Brilacidin-OM for Oral Mucositis Targeted to Begin in December 2014.
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Cellceutix Phase 2b Clinical Trial of Brilacidin Accepted for Oral Presentation at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).
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Cellceutix's Clinical Trial of Anti-Cancer Agent Kevetrin Meeting Its Goals, Approaching End of Trial.
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PolyMedix PMX-30063 Defensin-Mimetic Antibiotic Compound Shows Promising Activity for Oral Mucositis.
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New Data on PMX-30063 Presented at ASCO Suggest Strong Potential as Treatment for Oral Mucositis.
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PolyMedix Receives Grant From National Cancer Institute to Study Brilacidin for Oral Mucositis
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Cellceutix Files Orphan Drug Designation Application for Brilacidin for Oral Mucositis With US FDA.
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Innovation Pharmaceuticals Completes Dosing in Phase 1 Trial for New Oral Ulcerative Colitis Drug.
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Innovation Pharmaceuticals Announces Dose Escalation.
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Innovation Pharmaceuticals: Patient Screening for Phase 1 Trial of Oral Brilacidin in Ulcerative Colitis Program On Track for Early January.
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Innovation Pharmaceuticals Provides Update on Clinical Trials and Revenue Potential of Brilacidin in Inflammatory Bowel Diseases.
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Innovation Pharmaceuticals Announces Dosing of First Cohort in Phase 1 Trial of Oral Brilacidin in Ulcerative Colitis Program; Topline Results Anticipated Early Q1 2020.
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Innovation Pharmaceuticals Completes Treatments in Phase 2 PoC Trial for Induction of Remission in Inflammatory Bowel Disease; Topline Results with Endoscopic Response to Be Presented July 13, 2017.
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Cellceutix Releases Favorable Topline Findings as Part of Interim Analysis of Phase 2 Drug Candidate Brilacidin for the Treatment of Inflammatory Bowel Disease.
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Cellceutix Phase 2 Brilacidin Trial Progresses to Highest Dose Cohort for the Induction of Remission of Mild-to-Moderate Ulcerative Colitis.
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Cellceutixs Brilacidin Demonstrates Promise in Treating Ulcerative Colitis Supported by Endoscopic Assessment, Patient-Reported Outcomes.
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Cellceutix Completes Enrollment in Second of Three Planned Cohorts in Phase 2 Clinical Trial of Brilacidin for Inflammatory Bowel Disease.
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Cellceutix Phase 2 Trial Dose Escalates in 2nd Cohort for Brilacidin as a Novel Anti-Inflammatory Drug Candidate for Ulcerative Colitis.
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Cellceutix Receives Preliminary Approval for Clinical Trial of Brilacidin for Ulcerative Proctitis.
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Novocure Presents Interim STELLAR Results at IASLC Suggesting Treatment with Tumor Treating Fields Plus Chemotherapy may Extend Survival of Patients with Mesothelioma.
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Cellceutix Phase 2 Trial Initial Data Shows Potential of Brilacidin as a Novel Anti-Inflammatory Drug Candidate for the Induction of Remission of Mild-to-Moderate Ulcerative Colitis.
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Cellceutix Receives Update on First Patient Enrolled in Phase 2 Proof-of-Concept Study of Brilacidin for Ulcerative Proctitis.
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Phase II study of brilacidin for the treatment of Ulcerative Proctitis/Ulcerative Proctosigmoiditis (UP/UPS)
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Cellceutix Completes Patient Enrollment of Final Cohort in Phase 2 Trial of Brilacidin for Inflammatory Bowel Disease; Topline Results Anticipated in July.
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Cellceutix Releases Preliminary Efficacy and Safety Data in Interim Analysis of First Two Cohorts in Phase 2 Trial of Brilacidin for the Induction of Remission of Mild-to-Moderate Ulcerative Colitis.
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Innovation Pharmaceuticals Announces Successful Formulation of Oral Brilacidin Tablets; Upcoming Clinical Trial to Target Delivery to the Colon.
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Innovation Pharmaceuticals Provides Scientific Rationale and Clinical Development Perspectives for Brilacidin as a Potential Novel Coronavirus COVID-19 Treatment.
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Innovation Pharmaceuticals Submits Material Transfer Agreement to Study Lead Defensin Mimetic Brilacidin for Coronavirus (COVID-19).
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U.S. Regional Biocontainment Lab to Begin Testing of Brilacidin Against Coronavirus (COVID-19) Next Week.
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Innovation Pharmaceuticals Exploring Lead Defensin Mimetic Drug Candidate Brilacidin as Potential Novel Coronavirus Treatment.
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Cellceutix Novel Anti-Inflammatory Phase 2 Drug Candidate Brilacidin Builds Momentum Across Multiple Clinical Indications.
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Innovation Pharmaceuticals Brilacidin Franchise Anchored in Three Clinical Indications Oral Mucositis, Inflammatory Bowel Disease and Serious Skin Infections; Expands into Dermatologic Diseases.
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Innovation Pharmaceuticals Phase 2b Psoriasis Study On-Track for Completion in December 2017; Company a Sponsor at Upcoming Symposium on Hidradenitis Suppurativa.
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Cellceutix to Pursue Significant Conjuctivitis and Kerititis Ocular Markets With Novel Antibiotic Brilacidin.
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Cellceutix Plans for Entry in Diabetic Foot Wound and Ulcer Market.
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Cellceutix Provides Updates on Clinical Trials and Developments of Its Anti-Cancer, Anti-Psoriasis, and Antibiotic Compounds.
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Innovation Pharmaceuticals Collaborating with Regional Biocontainment Lab on Grant Application to Research Brilacidin as a Pan-Coronavirus Therapeutic.
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Innovation Pharmaceuticals Secures Up to $10 Million in Additional Financing to Advance Clinical Pipeline.
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Cellceutix Enters Into a $30 Million Common Stock Purchase Agreement.
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PolyMedix Announces Proposed Public Offering of Common Stock.
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PolyMedix Awarded Therapeutic Discovery Credits for Two Lead Programs.
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PolyMedix Antibiotic Studies Accepted for Presentation at ICAAC.
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PolyMedix Secures $14 Million Credit Facility and Files Shelf Registration Statement.
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Innovation Pharmaceuticals Provides Update on U.S. Patent Applications Covering Use of Brilacidin in Inflammatory Bowel Diseases, Coronaviruses and Fungal Diseases.
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Innovation Pharmaceuticals Receives New Patent for Compounds for Use in Treatment of Oral Mucositis.
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Innovation Pharmaceuticals Receives New Brilacidin Patent, Further Expanding Intellectual Property Estate.
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Innovation Pharmaceuticals Expands Brilacidin Patent Portfolio.
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Innovation Pharmaceuticals Granted European Patent for Brilacidin in the Prevention of Oral Mucositis.
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PolyMedix Receives U.S. Patent Protection for Licensed Computational Methods to Design Antimicrobial Polymers.
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PolyMedix Receives Issuance of Patent for Antimicrobial Compounds.
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Innovation Pharmaceuticals Plans for Phase 2 Trial of New Treatment for Ulcerative Colitis.
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Innovation Pharmaceuticals Brilacidin as a Novel Inhibitor of Phosphodiesterase 4 (PDE4) Supports its Potential to Treat Autoimmune and Inflammatory Diseases; Company Invited to Present at Upcoming Crohns & Colitis Foundation Conference.
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Innovation Pharmaceuticals Provides Corporate Update Highlighting Upcoming Milestones and Events.
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Innovation Pharmaceuticals Phase 2 PoC Trial for Inflammatory Bowel Disease Achieves Induction of Remission in a Majority of Patients Treated with Brilacidin.
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Innovation Pharmaceuticals Announces Clinical Development Plans for Oral Brilacidin for Inflammatory Bowel Disease.
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PolyMedix Announces Positive Results From Phase 2 Clinical Trial With PMX-30063 First-in-Class Defensin-Mimetic Antibiotic.
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PolyMedix's PMX-30063 First in Class Defensin-Mimetic Antibiotic Demonstrates Activity Against Drug-Resistant Bacterial Pathogens.
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PolyMedix Announces Encouraging Interim Results From Multinational Phase 2 Clinical Trial With PMX-30063 Defensin-Mimetic Antibiotic.
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Korczak B, McAllister E. A phase 1 trial to evaluate the tolerability, safety and pharmacokinetics of multi-dose intravenous regiments of PMX30063. 21st-ECCMID-27th-ICC-2011 2011; abstr. N/A.
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PolyMedix Defensin-Mimetic Antibiotic PMX-30063 Active Against NDM-1 Drug-Resistant Bacteria.
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Pulse ME. Efficacy of PMX30063 in Experimental Staphylococcal Skin and Skin Structure Infection Models. 49th-ICAAC 2009; abstr. F1-2013.
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Scott R W. Pharmacokinetic-Pharmacodynamic Relationships for PMX30063 in the Mouse Thigh Burden Model. 49th-ICAAC 2009; abstr. F1-2014.
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Scott RW, Liu D, Xu Y, Clements D, DeGrado WF. In vitro antimicrobial activities of a novel host defence protein mimetic, PMX30063, against multiple isolates of Saphylococci with defined susceptibility phenotypes. 48-ICAAC-46-IDSA-2008 2008;328 (plus poster) abstr. F1-3993.
Available from: URL: http://www.icaacidsa2008.org -
Scott RW, Korczak B, Clements D, Xu Y, Liu D. In vivo efficacy and safety of a novel host defecse protein mimetic, PMX30063: a candidate IV agent to treat Staphylococcal infections. 48-ICAAC-46-IDSA-2008 2008;328 (plus poster) abstr. F1-3994.
Available from: URL: http://www.icaacidsa2008.org -
Innovation Pharmaceuticals Clinical Trial of Oral Brilacidin in Ulcerative Colitis Program Expected to Commence in December; Top-Line Data in Q1 2020.
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Cellceutix Releases Confidence Interval Statistics Showing Clinical Success Rates for Brilacidin in Treatment of ABSSSI.
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Innovation Pharmaceuticals Plans for Clinical Trial of Oral Brilacidin for Ulcerative Colitis Program in 4th Quarter 2019.
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PolyMedix Presents PMX-30063 Antibiotic Data at the 49th Annual Meeting of the Infectious Disease Society of America.
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