Lots of talk about deals and financing and the like recently. Whenever this gets to be too much in my head, I like to get grounded in what is most familiar to me, the science. With that in mind, I am reposting this PR from 2018, just to get grounded. The limiting factor in many PDE4 inhibitors are side effects, mainly headache, vomiting and GI upset, thought to be due to the lack of specificity of the inhibition, resulting in inhibition of a variety of different isoforms of PDE4. It is quite interesting to me that Brilacidin has a low SE profile. Could this be due to its specificity? In my mind, unlikely. More likely is its global positive effect on immunoregulation and resultant anti-inflammation. Very excited about the possibilities.
BEVERLY, MA – October 12, 2018 (GLOBE NEWSWIRE) Innovation Pharmaceuticals, (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, is pleased to provide this update on Brilacidin as a novel inhibitor of Phosphodiesterase 4 (PDE4), an important aspect of its mechanism of action. PDE4 inhibitors, such as apremilast and crisaborole—the latter having been acquired by Pfizer in 2016 from Anacor—for dermatological conditions, are a well-established and actively marketed class of drugs used to treat a variety of autoimmune and inflammatory diseases. PDE4 inhibition is being studied as a novel therapeutic avenue in treating Inflammatory Bowel Disease (IBD).
Brilacidin’s Inhibition of PDE4
Due to multiple immunoregulatory functions, defensins—small antimicrobial peptides widely expressed and produced in skin and mucosal surfaces, as well as in neutrophils—play a critical role in mediating human health and disease. Brilacidin, the design of which was modeled on defensins, has been shown to be a potent regulator of immune response (data on file). It suppresses various pro-inflammatory mediators (e.g., TNF-α, IL-1β, IL-8, IL-6, MMP-9, MCP-1). One potentially central aspect of Brilacidin’s mechanism of action concerns its modulation of the cyclic adenosine monophosphate (cAMP) pathway, an established therapeutic target, through its ability to inhibit Phosphodiesterase 4 (PDE4) as well as Phosphodiesterase 3 (PDE3).
In more detail, pre-clinical studies have demonstrated that Brilacidin inhibits PDE4B2 and PDE3A in vitro, in a dose dependent manner. Brilacidin demonstrated similar IC50 values against both PDE4 (biochemical) and cytokine release in cell-based assays, suggesting Brilacidin has good cell membrane permeability. Localized clinical administration enables Brilacidin concentrations that markedly exceed in vitro IC50 values, and, consequently, provides for increased concentrations of cAMP.
The overall effect of Brilacidin’s ability to modulate cAMP levels—complementing other aspects of its broad immunomodulatory profile—supports its potential to treat a number of chronic, autoimmune and inflammatory diseases related to issues of innate immunity, such as: IBD, atopic dermatitis, and others.
While Brilacidin inhibition of PDE4, similar to multiple established FDA-approved drugs, contributes to its therapeutic potential, its pleiotropic actions likely offer additional unique advantages beneficial to multiple clinical applications.
Brilacidin for Inflammatory Bowel Disease
Reflective of Brilacidin’s treatment potential in IBD, the drug candidate has successfully been tested in a proof-of-concept study in distal colitis. Trial results showed that a majority of patients treated with Brilacidin achieved clinical remission, including mucosal healing as evidenced by endoscopic review. Plans include developing Brilacidin in an oral dosage form to treat more complex cases of IBD, such as Ulcerative Colitis and Crohn’s Disease.
As released previously, the Company has been asked, by invitation-only, to present at an upcoming IBD conference—“IBD Innovate 2018”—hosted by the Crohn’s & Colitis Foundation and scheduled for November 13, 2018. The scientific poster—titled “Brilacidin for Inflammatory Bowel Disease: A Novel, Non-Corticosteroid, Non-Biologic Drug Candidate in Clinical Development”—to be presented at the conference will be available in the Events and Presentations section of the Company website on November 13, 2018.
Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals, commented, “The results from our completed distal colitis study suggest Brilacidin could emerge as a novel, non-corticosteroid, and non-biologic, treatment for more extensive forms of bowel disease. We look forward to highlighting our data and sharing program insights at the IBD Innovate 2018 conference, attended by GI experts and pharmaceutical industry representatives.”
Linked below is additional information, published in a blog on the Company’s website, elaborating on how Brilacidin—given its unique and broad mechanism of action—is a promising candidate for continuing IBD drug development.
“Deficient Defensins and Missing Mucins in the Pathogenesis of Inflammatory Bowel Disease”
http://www.ipharminc.com/new-blog/2017/10/24/...el-disease
BEVERLY, MA – October 12, 2018 (GLOBE NEWSWIRE) Innovation Pharmaceuticals, (OTCQB:IPIX) (“the Company”), a clinical stage biopharmaceutical company, is pleased to provide this update on Brilacidin as a novel inhibitor of Phosphodiesterase 4 (PDE4), an important aspect of its mechanism of action. PDE4 inhibitors, such as apremilast and crisaborole—the latter having been acquired by Pfizer in 2016 from Anacor—for dermatological conditions, are a well-established and actively marketed class of drugs used to treat a variety of autoimmune and inflammatory diseases. PDE4 inhibition is being studied as a novel therapeutic avenue in treating Inflammatory Bowel Disease (IBD).
Brilacidin’s Inhibition of PDE4
Due to multiple immunoregulatory functions, defensins—small antimicrobial peptides widely expressed and produced in skin and mucosal surfaces, as well as in neutrophils—play a critical role in mediating human health and disease. Brilacidin, the design of which was modeled on defensins, has been shown to be a potent regulator of immune response (data on file). It suppresses various pro-inflammatory mediators (e.g., TNF-α, IL-1β, IL-8, IL-6, MMP-9, MCP-1). One potentially central aspect of Brilacidin’s mechanism of action concerns its modulation of the cyclic adenosine monophosphate (cAMP) pathway, an established therapeutic target, through its ability to inhibit Phosphodiesterase 4 (PDE4) as well as Phosphodiesterase 3 (PDE3).
In more detail, pre-clinical studies have demonstrated that Brilacidin inhibits PDE4B2 and PDE3A in vitro, in a dose dependent manner. Brilacidin demonstrated similar IC50 values against both PDE4 (biochemical) and cytokine release in cell-based assays, suggesting Brilacidin has good cell membrane permeability. Localized clinical administration enables Brilacidin concentrations that markedly exceed in vitro IC50 values, and, consequently, provides for increased concentrations of cAMP.
The overall effect of Brilacidin’s ability to modulate cAMP levels—complementing other aspects of its broad immunomodulatory profile—supports its potential to treat a number of chronic, autoimmune and inflammatory diseases related to issues of innate immunity, such as: IBD, atopic dermatitis, and others.
While Brilacidin inhibition of PDE4, similar to multiple established FDA-approved drugs, contributes to its therapeutic potential, its pleiotropic actions likely offer additional unique advantages beneficial to multiple clinical applications.
Brilacidin for Inflammatory Bowel Disease
Reflective of Brilacidin’s treatment potential in IBD, the drug candidate has successfully been tested in a proof-of-concept study in distal colitis. Trial results showed that a majority of patients treated with Brilacidin achieved clinical remission, including mucosal healing as evidenced by endoscopic review. Plans include developing Brilacidin in an oral dosage form to treat more complex cases of IBD, such as Ulcerative Colitis and Crohn’s Disease.
As released previously, the Company has been asked, by invitation-only, to present at an upcoming IBD conference—“IBD Innovate 2018”—hosted by the Crohn’s & Colitis Foundation and scheduled for November 13, 2018. The scientific poster—titled “Brilacidin for Inflammatory Bowel Disease: A Novel, Non-Corticosteroid, Non-Biologic Drug Candidate in Clinical Development”—to be presented at the conference will be available in the Events and Presentations section of the Company website on November 13, 2018.
Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals, commented, “The results from our completed distal colitis study suggest Brilacidin could emerge as a novel, non-corticosteroid, and non-biologic, treatment for more extensive forms of bowel disease. We look forward to highlighting our data and sharing program insights at the IBD Innovate 2018 conference, attended by GI experts and pharmaceutical industry representatives.”
Linked below is additional information, published in a blog on the Company’s website, elaborating on how Brilacidin—given its unique and broad mechanism of action—is a promising candidate for continuing IBD drug development.
“Deficient Defensins and Missing Mucins in the Pathogenesis of Inflammatory Bowel Disease”
http://www.ipharminc.com/new-blog/2017/10/24/...el-disease
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