News & Events zu Propanc Biopharma Inc (PPCB)PPCBPropanc Biopharma Inc

Propanc Biopharma Develops New Pancreatic Enzyme, Significantly Reduces Cancer Cell Proliferation

Propanc Biopharma announced highlighted new preclinical findings evaluating its pancreatic proenzyme formulation, or PRP, alone and in combination with galunisertib, or GAL, a small-molecule inhibitor of transforming growth factor beta receptor I, or TGF-betaRI, in pancreatic ductal adenocarcinoma, or PDAC, models. The company has filed an Australian patent application relating to the combination approach. The research was conducted in collaboration with investigators at the University of Jaen and the University of Granada in Spain. The study compared PRP, GAL and PRP plus GAL in wild-type BxPC-3 pancreatic cancer cells, gemcitabine-resistant BxPC-3 cells, normal-associated fibroblasts, or NAFs, and cancer-associated fibroblasts, or CAFs. Experiments assessed cell proliferation, colony formation, migration and invasion, together with molecular readouts associated with TGF-beta signaling, epithelial-mesenchymal transition, or EMT, extracellular-matrix, or ECM, remodeling and fibroblast activation. TGF-beta signaling can contribute to tumor-cell plasticity, EMT and stromal activation, although its effects depend on cellular context. The study investigated whether PRP could modulate these tumor- and stroma-associated processes and whether adding a TGF-beta pathway inhibitor provided further effects. PRP reduced cell proliferation by approximately 50% in wild-type and gemcitabine-resistant BxPC-3 cells relative to untreated controls. PRP plus GAL reduced proliferation by 75% and 66%, respectively. The additional reduction versus PRP alone was significant in wild-type cells; in resistant cells, the further reduction was not statistically significant. PRP reduced colony formation by 59% in wild-type cells and 39% in gemcitabine-resistant cells. The combination reduced colony formation by 68% and 64%, respectively. The additional effect of the combination over PRP alone was significant in the resistant model, but not in the wild-type model. In wound-healing assays at 72 hours, wound closure was 21% with PRP in wild-type cells and 57% in resistant cells, compared with untreated controls. PRP plus GAL resulted in 19% and 30% wound closure, respectively; the combination significantly improved the result over PRP alone in resistant cells, but not in wild-type cells. In Matrigel invasion assays, PRP reduced invasion by 81% in wild-type cells and 47% in resistant cells. PRP plus GAL produced reductions of 89% and 80%, respectively. PRP significantly reduced SMAD2, SMAD3 and TGFBR1 transcript levels to 0.45-, 0.63- and 0.55-fold of control in wild-type cells, and to 0.42-, 0.36- and 0.23-fold in resistant cells, compared to control group. The combination produced further reductions in selected readouts, although the magnitude and statistical significance of the additional effects varied across models and markers. PRP increased E-cadherin expression 5.29-fold in wild-type cells and 4.86-fold in resistant cells, while reducing Vimentin to 0.31- and 0.32-fold and Snail to 0.62- and 0.28-fold, respectively, relative to untreated controls. The combination produced additional changes in selected biomarkers, including stronger suppression of Snail in the resistant-cell model. These transcriptional findings are consistent with a shift towards a more epithelial gene-expression profile; they do not establish complete reversal of EMT. In wild-type cells, PRP reduced MYC and SOX2 expressions to 0.27- and 0.54-fold of control, respectively, and increased the pro-apoptotic marker BAX 2.49-fold. In resistant cells, MYC and SOX2 fell to 0.11- and 0.22-fold, while BAX increased 2.74-fold. These are gene-expression results and can be interpreted as degree of apoptosis. PRP reduced CAF proliferation by up to 53% and CAF invasion by 85%, while its effect on NAF proliferation was modest and not statistically significant; NAF invasion was reduced by 19%. The gene-expression data showed a similar differential response. In CAFs, PRP reduced alphaSMA, FAPalpha and YAP1 expression to 0.56-, 0.27- and 0.58-fold of untreated-control levels, respectively. It also reduced COL1A1, FN1, MMP9, IL6 and CXCL12 expressions to 0.65-, 0.42-, 0.49-, 0.25- and 0.54-fold of control, respectively. In NAFs, the corresponding reductions in COL1A1, FN1, MMP9, IL6 and CXCL12 expression were not statistically significant; alphaSMA expression was 0.81-fold of control, YAP1 was 0.89-fold, and FAPalpha expression was undetectable. Overall, the pattern suggests a more pronounced effect on activated CAFs than on NAFs. Compared with PRP monotherapy, the addition of GAL enhanced the inhibition of selected CAF-associated functional and molecular features, although it also increased the impact on normal-associated fibroblasts. In proliferation assays PRP + GAL reduced CAF proliferation by 71%, compared with 53% with PRP alone, while inhibition in NAFs increased from a non-significant 22% with PRP to 55% with the combination. In clonogenic assays, the combination reduced colony formation by 78% in CAFs, compared with 69% with PRP alone; however, it also reduced NAF clonogenic capacity by 42%, whereas PRP largely preserved it. This additional reduction in NAF clonogenicity was significant, while the additional reduction in CAFs was not significant. Regarding migration, PRP + GAL limited wound closure in CAFs to 28% at 72 hours, compared with 35% with PRP alone, whereas NAF wound closure reached 100% under both treatment conditions. In Matrigel assays, the combination further reduced invasion in CAFs from 85% with PRP alone to 90%, while the reduction in NAF invasion increased from 19% to 32%. At the molecular level, PRP + GAL produced a slightly greater downregulation of CAF-associated genes than PRP alone, reducing COL1A1, FN1, MMP9, IL6 and CXCL12 expression to 0.40-, 0.32-, 0.29-, 0.16- and 0.32-fold of control levels, respectively, compared with 0.65-, 0.42-, 0.49-, 0.25- and 0.54-fold with PRP alone. The combination also reduced CAF activation markers alphaSMA and FAPalpha to 0.45- and 0.19-fold of control, respectively, compared with 0.46- and 0.30-fold with PRP. In NAFs, the combination reduced COL1A1, FN1, MMP9, IL6 and CXCL12 expressions to 0.63-, 0.85-, 0.56-, 0.68- and 0.80-fold of control, respectively, indicating broader effects than PRP monotherapy, for which these changes were modest and not statistically significant. Overall, PRP alone showed a more favorable stromal selectivity profile, whereas the addition of GAL enhanced suppression of several CAF-associated markers but also increased effects on NAF proliferation, clonogenicity and invasion.

Propanc Biopharma Advances PRP Clinical Development Program

Propanc Biopharma announced it is advancing its clinical development program for PRP, its investigational proenzyme-based therapeutic candidate, as preparations continue for its planned Phase 1b, first-in-human study in up to 50 advanced cancer patients with solid tumors. The current project schedule targets the first-site ethics submission process during November, followed by regulatory activities in January 2027. Propanc currently targets February 2027 for its first clinical site initiation visit followed by its first patient screening.

Propanc Biopharma Releases PRP Preclinical Data Showing Potential Against Chemotherapy Resistance in Pancreatic Cancer

Propanc Biopharma announced new preclinical data supporting the potential of its lead asset, PRP, to address chemotherapy resistance in pancreatic cancer. In collaborative research led by Maria Belen Toledo at the Universities of Jaen and Granada, PRP was shown to remodel the resistant cellular state in pancreatic cancer models with acquired chemotherapy resistance. The study used a sequential design and demonstrated that PRP functions as a resistance-modulating intervention rather than a conventional cytotoxic agent. Key preclinical findings: proliferation and survival: PRP monotherapy reduced cancer cell proliferation by approximately 50-54% and suppressed long-term clonogenic survival by up to 59%. Migration limited to 21-57% wound closure; invasive capacity reduced by 47%-81%. Strong epithelial differentiation with E-cadherin upregulated up to 5.29-fold and EPCAM up to 4.39-fold; mesenchymal drivers Vimentin reduced to ~0.31-0.32-fold and Snail to 0.28-0.62-fold. Significant downregulation of TGF-ss/SMAD signaling, induction of pro-apoptotic BAX, and suppression of oncogenic stemness drivers MYC and SOX2. PRP plus TGF-ss inhibition further amplified responses, including 80% invasion inhibition and stronger apoptotic signaling. These results complement the company's recent peer-reviewed pilot study published in Scientific Reports, which reported an 85.9% reduction in mean tumor weight in an orthotopic pancreatic model at the higher dose, approximately 50% tumor-weight inhibition in an ovarian model, anti-angiogenic activity, near-complete blockade of invasion in select lines, and EMT reversal. The Pan 02 cancer cell line is particularly noteworthy since it is a syngeneic tumor model conducted in immunocompetent mice and is clinically relevant for patients where cytotoxic agents induce immunosuppression and are at risk of infection-one of the main causes of death for cancer patients. Conversely, PRP reduces chemoresistance whilst enhancing immunorecognition. In addition, earlier orthotopic and patient-derived xenograft data have also shown greater than 90% mean tumor growth inhibition and greater than 2.5-fold median survival extension in advanced PDAC models, with reduced metastatic burden and tumor microenvironment remodeling.