Panacea Pharmaceuticals, a clinical stage biopharmaceutical company developing novel biologically targeted cancer therapies and diagnostics for unmet medical needs, has announced that the first patient has been enrolled and dosed in the open-label, parallel designed, multicenter phase I clinical trial of PAN-301-1 for the treatment of persistent prostate cancer to assess safety and immunogenicity. Clinical sites for the PAN-301-1 trial are located in Alabama, California, Nebraska and South Carolina and the trial is managed by Accelovance.

PAN-301-1, a novel, HAAH-directed nanoparticle immunotherapy vaccine candidate, functions as an immune stimulator nanoparticle with hundreds of copies of an HAAH fragment on the surface of the nanoparticle. This vaccine is highly immunogenic and produces an HAAH-specific antibody response and significantly stimulates immune cells to target HAAH. 

HAAH, human aspartyl (asparaginyl) β-hydroxylase (HAAH) or aspartate β-hydroxylase (ASPH), is an enzyme that is normally expressed in fetal development, where it plays a role in cell growth, movement and cell-cell interaction in tissues during formation. At the time of birth, the gene is silenced. However, in adults, expression of HAAH is uniquely associated with cancer and is related to cancer cell growth, cell motility and invasiveness. In cancer cells, HAAH is only expressed on the surface of the cells and has been detected in more than 20 different types of cancer. HAAH expression levels are inversely correlated with disease prognosis. When normal cells are transfected with the HAAH gene, they behave like cancer cells and when HAAH is inhibited in cancer cells, they behave like normal cells.

"Based on data from the American Cancer Society, there are more than 160,000 cases of prostate cancer anticipated in 2017 and approximately 30% of men treated will relapse after five years, with limited treatment options for patients living with persistent prostate cancer," said Luke Nordquist, M.D., GU Research Network in Omaha, Neb. and Lead Principal Investigator for the study. "HAAH provides a new potential treatment pathway for patients living with persistent prostate cancer, and with the enrollment of the first patient at our center, we are eager to understand the safety and immunogenicity for PAN-301-1 to address this unmet medical need in cancer diagnosis and treatment."

In the phase I trial, PAN-301-1 will be administered through intradermal injection in cohorts of patients with biochemically relapsed prostate cancer, using a fixed dose-escalation schema every 21 days to establish the recommended phase II dose, with an opportunity to extend the study at the same dose. Approximately 18 patients will be enrolled and studied.

"At Panacea, we have created a promising new vaccine therapy drug candidate that targets a specific and novel cancer-relevant marker, overcoming self-tolerance, yet avoiding autoimmune-like side effects of check-point inhibitors throughout our pre-clinical studies," said Hossein A. Ghanbari, Ph.D., president, chief executive officer and chief science officer, Panacea Pharmaceuticals. "The initiation of the phase I PAN-301-1 serves as a starting point for utilizing HAAH in treatment to prevent the recurrence of cancer. We are excited to explore this new targeted biological pathway in cancer."

In animal models of cancer using immune competent mice and rats, which have an HAAH sequence and expression similar to humans, the PAN-301-1 HAAH vaccine has significantly inhibited tumor growth and metastasis, and has enhanced survival, compared to non-treated animals. The vaccine has also been demonstrated as safe in a preclinical, multiple-dose toxicology study, which contrasts with the significant side effects that are present in current cancer therapies.