Propanc Biopharma Engages European CDMO for GMP Production of PRP for Phase 1b, FIH Study in 30 – 40 Advanced Cancer Patients

Propanc Biopharma Secures CDMO for PRP's Phase 1b FIH Study

Propanc Biopharma, Inc. has engaged a European Contract and Development Manufacturing Organization (CDMO) for the GMP production of its lead asset, PRP. This manufacturing is crucial for the upcoming Phase 1b, First-In-Human (FIH) study, which will enroll 30–40 advanced cancer patients suffering from solid tumors. The company plans to file the clinical trial application later this year, aiming to enter early-stage clinical development for PRP, a proenzyme therapy administered once weekly intravenously. PRP previously received Orphan Drug Designation from the USFDA for pancreatic cancer in 2017.

• Propanc Biopharma has secured a European CDMO to handle the GMP manufacturing of PRP, its lead proenzyme therapy. This partnership is a critical step to ensure the supply of PRP for the planned Phase 1b, First-In-Human clinical study, which is expected to commence after the clinical trial application is filed later this year.
• The upcoming Phase 1b FIH study will investigate PRP in 30–40 advanced cancer patients with solid tumors, administered once weekly intravenously. This trial represents a significant advancement for PRP, which is believed to be a first-in-class proenzyme therapy aiming to induce cancer cell differentiation rather than direct killing.
• PRP holds Orphan Drug Designation status from the US FDA for the treatment of pancreatic cancer, granted in 2017. This designation highlights the potential of PRP to address an unmet medical need and could offer certain incentives and benefits during its development and regulatory review process.

Navigating Current Treatment Limitations for Advanced Solid Tumors

Current treatment approaches for advanced solid tumors face substantial challenges that limit therapeutic success and patient outcomes. Traditional modalities including radiotherapy, chemotherapy, and targeted agents remain predominantly palliative, offering only modest survival improvements while carrying significant toxicity burdens. These limitations underscore the urgent need for novel therapeutic strategies to improve clinical outcomes.

• Limited efficacy of conventional therapies - Standard cancer therapy for solid tumors may have reached a therapeutic plateau, with conventional chemotherapeutic regimens demonstrating limited impact against most advanced solid tumors and long-term survival rates remaining low for most patients

• Treatment-related toxicity and quality of life impact - Chemotherapy and radiation therapy are associated with significant toxicity that severely affects patients' physical, emotional, and social well-being, with adverse effects from traditional treatments including radical surgery and systemic chemotherapy seriously impacting survival quality

• Development of therapeutic resistance - Overcoming resistance to therapy has become a major challenge, with solid tumors developing robust drug resistance mechanisms through complex molecular processes that are not yet fully understood, while efficient DNA repair in cancer cells serves as an important mechanism for therapeutic resistance

• Tumor microenvironment barriers - Solid tumors remain difficult to treat due to antigen heterogeneity, physical barriers that limit immune-cell trafficking, and a profoundly immunosuppressive tumor microenvironment that impedes therapeutic effectiveness

• Limited immunotherapy responsiveness - Many solid tumors are classified as non-inflamed, meaning they are less responsive to immunotherapies compared to hematologic malignancies, with CAR-T cell therapy showing less encouraging clinical results in solid tumors compared to up to 90% complete remission rates in B-cell acute lymphoblastic leukemia

• Metastasis and disease progression - Metastasis remains the major cause of cancer-related morbidity and mortality, with limited strategies available to reduce the risk of recurrence of primary tumors or development of second cancers among survivors

• Treatment selection complexity - First-generation positive trials for particular disease sites are often accomplished with vastly differing treatment regimens, leaving oncologists to question which specific approach is optimal for individual patients

Is PRP Truly a First-in-Class Proenzyme Therapy?

Anti-cytokine drugs (biotherapies) are being trialled for neuropathic pain conditions, sharing a similar mechanism of action with PRP through cytokine modulation and targeting the neuroinflammation network. Both therapeutic approaches work by modulating cytokines secreted by immune cells and glial cells, though PRP provides an indirect approach through growth factors while anti-cytokine drugs target cytokines directly.

PRP's Phase 1b Entry: A New Antiangiogenic Frontier in Solid Tumors

Propanc Biopharma's move to initiate a Phase 1b First-In-Human (FIH) study for its lead asset, PRP, marks a significant milestone in the pursuit of novel cancer therapies. This proenzyme therapy, administered intravenously once weekly, is designed to target advanced solid tumors, building on preclinical evidence suggesting its role as a potent angiostatic agent. The engagement of a European CDMO for GMP production is a critical step, ensuring the quality and scalability necessary for clinical development.

The strategic implications of this advancement are noteworthy. Firstly, if successful, PRP could offer a new therapeutic option for patients with advanced solid tumors, particularly those with pancreatic cancer, for which it has already received Orphan Drug Designation. This designation underscores the high unmet medical need and could accelerate regulatory pathways. Secondly, the intravenous, once-weekly dosing schedule could enhance patient convenience and adherence, a crucial factor for long-term cancer management. Finally, the robust manufacturing partnership de-risks the supply chain for this protein-based therapeutic, a common challenge in early-stage development.

However, several considerations warrant attention as PRP progresses. The preclinical data, while promising, were derived from adenovirus-mediated gene delivery of proliferin-related protein (PRP) in murine models. Translating this to a directly administered proenzyme therapy in humans introduces inherent uncertainties regarding pharmacokinetics, pharmacodynamics, and overall efficacy in a diverse patient population with advanced solid tumors. The broad classification as a "proenzyme therapy" also suggests a need for further elucidation of its precise mechanism of action beyond its antiangiogenic properties to fully understand its therapeutic potential and safety profile in humans. The journey from preclinical promise to clinical success is arduous, and the upcoming Phase 1b study will be pivotal in establishing the safety and initial signals of efficacy for this intriguing antiangiogenic candidate.