Protox Therapeutics, a product-focused development-stage company, has acquired a phase II clinical stage programme for the treatment of cancer from Neurocrine Biosciences Inc. and the US Public Health Service (PHS).
The targeted, therapeutic toxin PRX321, formerly known as NBI-3001, has received both Fast Track Designation and Orphan Drug Status from the US Food and Drug Administration (FDA) for primary brain tumours. Fast Track Designation enables expedited review by the FDA of products that are in clinical development and Orphan Drug Status provides a number of benefits including seven years of market exclusivity.
"We have substantially expanded our clinical pipeline with the acquisition of PRX321 and view this transaction as accelerating our path toward becoming the world leader in the development of targeted toxin therapeutics", stated Dr Fahar Merchant, President and CEO of Protox. "This transaction transforms Protox into a company, with a robust clinical pipeline targeting serious indications such as brain, kidney, prostate and lung cancers that have large unmet medical needs. Furthermore, the acquisition of PRX321 provides us with encouraging human clinical data from 86 cancer patients, a strengthened intellectual property portfolio of 14 patents, issued worldwide and a technology, which is supported by over 50 peer-reviewed scientific publications."
PRX321 is a targeted therapeutic toxin, in which a cytokine, interleukin-4 (IL-4), is linked to a Pseudomonas exotoxin, a potent substance that can destroy cancer cells. The IL-4 portion of the compound binds to IL-4 receptors found on the surface of various types of cancer cells. The drug subsequently enters the target cell where the toxin component causes cell death by inhibiting protein synthesis.
Besides brain, kidney and lung cancer, PRX321 has shown promising pre-clinical results in a number of cancers over-expressing IL-4 receptors including pancreatic, ovarian, breast, head and neck, melanoma, prostate and blood cancers such as chronic lymphocytic leukaemia (CLL) and Hodgkin's lymphoma.
In phase I and II clinical trials for the treatment of primary brain cancers, namely, glioblastoma multiforme (GBM) and anaplastic astrocytoma, patients were administered PRX321 intra-tumorally. Results from these studies demonstrated potent anti-tumour effects without drug-related systemic toxicity in the majority of patients.
Protox plans to conduct a phase II, dose-refining clinical trial to optimize the dose for PRX321 in patients, with primary brain cancer. In another phase I study, patients with recurrent or unresponsive metastatic renal cell and non-small cell lung carcinomas were administered escalating doses of PRX321 intravenously to determine the maximum tolerated dose.
The PRX321 programme was acquired by Protox in two separate transactions. In the first transaction, Protox obtained exclusive worldwide rights to IL-4 fusion toxin technology (INxinTM) from PHS. In the second transaction, regulatory and product assets were purchased from Neurocrine in order to facilitate the continued development of PRX321.
The assets purchased from Neurocrine included two Investigational New Drug applications, Fast Track Designation and Orphan Drug Status, as well as cGMP batches of PRX321 that may potentially be used in future clinical trials. The IL-4 fusion toxin was originally discovered and developed by Dr Raj Puri, from the Centre for Biologics Evaluation and Research of the FDA and colleagues from the National Cancer Institute (NCI). Subsequent development and clinical studies were sponsored by Neurocrine and additional research continues at the FDA and NCI under the direction of Dr Puri.
Protox has committed to pay PHS and Neurocrine, for the license and corresponding assets, up to US$2 million over the next three years. In addition, Protox will pay PHS up to US$4 million in future milestone payments (based on the compound receiving FDA approval for at least three indications), as well as royalties on commercial sales.