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Posted On: 10/04/2022 12:13:17 PM
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Innovation Pharmaceuticals Announces Publication of Scientific Article on the Antifungal Activity of Brilacidin
In pre-clinical studies, Brilacidin shown to synergize with marketed antifungals against pathogenic species of aspergillosis, candidiasis, cryptococcosis and mucormycosis, and further exhibited potent stand-alone efficacy against Cryptococcus neoformans
These data suggest Brilacidin has potential as a novel antifungal agent
WAKEFIELD, MA / October 4, 2022 Innovation Pharmaceuticals (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, today announced publication of a scientific article on the antifungal activity of Brilacidin, the Company’s defensin-mimetic drug candidate with antimicrobial and immunomodulatory properties. The paper, accessible at the link below as a preprint and to be submitted for peer review, is based on independent research conducted primarily by scientists at the University of São Paulo, Brasil. A corresponding patent application related to this work has been filed.
Fernanda dos Reis T, Alves de Castro P, Bastos R, Pinzan CF, Souza PFN, Ackloo S, Hossain MA, Drewry D, Alkhazraji S, Ibrahim A, Hyunil J, DeGrado WF. “A Host Defense Peptide Mimetic, Brilacidin, Potentiates Caspofungin Antifungal Activity Against Human Pathogenic Fungi.”
bioRxiv 2022.09.28.509882; doi.org/10.1101/2022.09.28.509882
Summary of Brilacidin Antifungal Research Findings
Following an in vitro drug screening of 1,402 compounds, Brilacidin showed promising antifungal activity and was subsequently selected for additional pre-clinical evaluation, including in combination with caspofungin (CAS), voriconazole (VOR), and posaconazole (POSA), all current antifungal treatments.
In cell culture, in Aspergillus fumigatus (A. fumigatus), Brilacidin converted CAS from a fungistatic into a fungicidal drug, enabling it to overcome both drug resistance and biofilm formation. 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. Mortality rates can be as high as 90 percent in this fungal disease.
Interestingly, Brilacidin showed potent in vitro stand-alone efficacy (MIC=2.5µM) in C. neoformans, a major driver of illness in people living with HIV/AIDS. C. neoformans, for which few effective treatments are available, causes an estimated 220,000 cases of cryptococcal meningitis worldwide each year and is associated with an 80 percent mortality rate.
A proposed antifungal mechanism of action of Brilacidin involves membrane depolarization by impacting calcineurin and cell wall integrity, as informed by protein kinase inhibitory experiments and genetic screenings of protein phosphatase null mutants.
“It is a remarkable feature of Brilacidin that it can potentiate multiple antifungals, in different pathogenic fungi, including hard-to-treat species. New antifungal combination strategies are urgently needed due to a scarcity of novel agents, alongside emerging resistance in the clinical setting,” commented Gustavo Henrique Goldman, Professor of Molecular Biology, University of São Paulo, Brasil, and a Chief Editor for Frontiers in Fungal Biology, a peer-reviewed journal dedicated to the study of mycology. “Another notable finding from our research is that Brilacidin shows exceptional potency of its own as a monotherapy against C. neoformans, a particularly problematic fungus. We look forward to broadening our planned studies of Brilacidin’s antifungal properties.”
About Antifungal Diseases
There are up to 5 million fungal species populating the earth, of which approximately 100,000 species have been identified. About 300 fungal species cause disease in humans. Overall, Candida, Cryptococcus and Aspergillus represent the main causative organisms of invasive fungal infections. There is a large unmet medical need for developing novel antifungal agents, particularly given the emergence of resistance in the clinical setting. The utility of current antifungal treatments is limited due to toxicity, fungistatic and not fungicidal properties, as well as drug interaction concerns. In the United States, antifungal drugs can qualify for expedited clinical development, under Qualified Infectious Disease Product designation, Orphan Drug designation, and the limited population pathway development program. Pivotal clinical trials for antifungal drugs are generally smaller than those in other infectious disease areas, requiring between 300 and 600 patients. Caspofungin sales were estimated to be $414 million in 2021, with the global antifungal drugs market estimated at $14.8 billion in 2021 and expected to reach $20.5 billion by 2030.
1 Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy
2 Global Caspofungin Market Research Report 2022 (Status and Outlook)
3 Antifungal Drugs Market Size to be worth $20.5 Billion by 2030: Grand View Research, Inc.
About Innovation Pharmaceuticals
Innovation Pharmaceuticals Inc. (IPIX) is a clinical stage biopharmaceutical company developing a portfolio of innovative therapies addressing multiple areas of unmet medical need, including inflammatory diseases, cancer, and infectious diseases. The Company is also active in evaluating other potential investment opportunities that can add value and diversify its portfolio.
In pre-clinical studies, Brilacidin shown to synergize with marketed antifungals against pathogenic species of aspergillosis, candidiasis, cryptococcosis and mucormycosis, and further exhibited potent stand-alone efficacy against Cryptococcus neoformans
These data suggest Brilacidin has potential as a novel antifungal agent
WAKEFIELD, MA / October 4, 2022 Innovation Pharmaceuticals (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, today announced publication of a scientific article on the antifungal activity of Brilacidin, the Company’s defensin-mimetic drug candidate with antimicrobial and immunomodulatory properties. The paper, accessible at the link below as a preprint and to be submitted for peer review, is based on independent research conducted primarily by scientists at the University of São Paulo, Brasil. A corresponding patent application related to this work has been filed.
Fernanda dos Reis T, Alves de Castro P, Bastos R, Pinzan CF, Souza PFN, Ackloo S, Hossain MA, Drewry D, Alkhazraji S, Ibrahim A, Hyunil J, DeGrado WF. “A Host Defense Peptide Mimetic, Brilacidin, Potentiates Caspofungin Antifungal Activity Against Human Pathogenic Fungi.”
bioRxiv 2022.09.28.509882; doi.org/10.1101/2022.09.28.509882
Summary of Brilacidin Antifungal Research Findings
Following an in vitro drug screening of 1,402 compounds, Brilacidin showed promising antifungal activity and was subsequently selected for additional pre-clinical evaluation, including in combination with caspofungin (CAS), voriconazole (VOR), and posaconazole (POSA), all current antifungal treatments.
In cell culture, in Aspergillus fumigatus (A. fumigatus), Brilacidin converted CAS from a fungistatic into a fungicidal drug, enabling it to overcome both drug resistance and biofilm formation. 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. Mortality rates can be as high as 90 percent in this fungal disease.
Interestingly, Brilacidin showed potent in vitro stand-alone efficacy (MIC=2.5µM) in C. neoformans, a major driver of illness in people living with HIV/AIDS. C. neoformans, for which few effective treatments are available, causes an estimated 220,000 cases of cryptococcal meningitis worldwide each year and is associated with an 80 percent mortality rate.
A proposed antifungal mechanism of action of Brilacidin involves membrane depolarization by impacting calcineurin and cell wall integrity, as informed by protein kinase inhibitory experiments and genetic screenings of protein phosphatase null mutants.
“It is a remarkable feature of Brilacidin that it can potentiate multiple antifungals, in different pathogenic fungi, including hard-to-treat species. New antifungal combination strategies are urgently needed due to a scarcity of novel agents, alongside emerging resistance in the clinical setting,” commented Gustavo Henrique Goldman, Professor of Molecular Biology, University of São Paulo, Brasil, and a Chief Editor for Frontiers in Fungal Biology, a peer-reviewed journal dedicated to the study of mycology. “Another notable finding from our research is that Brilacidin shows exceptional potency of its own as a monotherapy against C. neoformans, a particularly problematic fungus. We look forward to broadening our planned studies of Brilacidin’s antifungal properties.”
About Antifungal Diseases
There are up to 5 million fungal species populating the earth, of which approximately 100,000 species have been identified. About 300 fungal species cause disease in humans. Overall, Candida, Cryptococcus and Aspergillus represent the main causative organisms of invasive fungal infections. There is a large unmet medical need for developing novel antifungal agents, particularly given the emergence of resistance in the clinical setting. The utility of current antifungal treatments is limited due to toxicity, fungistatic and not fungicidal properties, as well as drug interaction concerns. In the United States, antifungal drugs can qualify for expedited clinical development, under Qualified Infectious Disease Product designation, Orphan Drug designation, and the limited population pathway development program. Pivotal clinical trials for antifungal drugs are generally smaller than those in other infectious disease areas, requiring between 300 and 600 patients. Caspofungin sales were estimated to be $414 million in 2021, with the global antifungal drugs market estimated at $14.8 billion in 2021 and expected to reach $20.5 billion by 2030.
1 Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy
2 Global Caspofungin Market Research Report 2022 (Status and Outlook)
3 Antifungal Drugs Market Size to be worth $20.5 Billion by 2030: Grand View Research, Inc.
About Innovation Pharmaceuticals
Innovation Pharmaceuticals Inc. (IPIX) is a clinical stage biopharmaceutical company developing a portfolio of innovative therapies addressing multiple areas of unmet medical need, including inflammatory diseases, cancer, and infectious diseases. The Company is also active in evaluating other potential investment opportunities that can add value and diversify its portfolio.
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