Adva-27a
Our Flagship Anticancer Drug
Our flagship anticancer compound is Adva-27a, a GEM-difluorinated C-glycoside derivative of Podophyllotoxin, targeted for various forms of cancer (See 3D Molecular Model below). Adva-27a is expected to enter Phase I clinical trials for pancreatic cancer and multidrug resistant breast cancer following completion of the GMP manufacturing and formulation of a 2-kilograms quantity for injection. The mechanism by which Adva-27a is able to destroy cancer cells is through the inhibition of a key cell-cycle enzyme called Topoisomerase II. Unlike other antitumor drugs currently in use, Adva-27a is able to destroy multidrug resistant cancer cells. Adva-27a is very effective against multidrug resistant breast cancer cells, while Etoposide, another Topoisomerase II inhibitor, has no activity against this aggressive form of cancer (see Figure below). In other studies, Adva-27a showed cell killing activity in various other types of multidrug resistant cancer cells.
Our preclinical studies to date have shown that:
- Adva-27a is effective at killing different types of multidrug resistant cancer cells, including:
- Breast Cancer Cells (MCF-7/MDR)
- Small Cell Lung Cancer Cells (H69AR)
- Uterine Cancer (MES-SA/Dx5)
- Pancreatic Cancer (Panc-1)
- Adva-27a is unaffected by P-Glycoprotein, the enzyme responsible for making cancer cells resistant to anti-tumour drugs.
- Adva-27a has excellent clearance time (half-life = 54 minutes), as indicated by human microsomes stability studies and pharmacokinetics data in rats.
- Adva-27a clearance is independent of Cytochrome P450, a mechanism that is less likely to produce toxic intermediates.
- Adva-27a is an excellent inhibitor of Topoisomerase II with an IC50 of only 13.7 micromolar (this number has recently been reduced to 1.44 micromolar as a result of resolving the two isomeric forms of Adva-27a).
- Adva-27a has shown an excellent pharmacokinetic profile, as indicated by studies done in rats.
- Adva-27a does not inhibit tubulin assembly.
Adva-27a Molecule in 3D
Adva-27a Publication
These and other preclinical data have been published in ANTICANCER RESEARCH, a peer-reviewed International Journal of Cancer Research and Treatment. The manuscript entitled “Adva-27a, a Novel Podophyllotoxin Derivative Found to Be Effective Against Multidrug Resistant Human Cancer Cells” appeared in print in the October 2012 issue of the journal [ANTICANCER RESEARCH 32: 4423-4432 (2012)]. The following is a link to a copy of the full manuscript as it appeared in the journal (PDF).
Adva-27a Clinical Trials Plans
Adva-27a’s initial indication for Phase I clinical trials will be pancreatic cancer. We are planning to conduct our clinical trials at McGill University’s Jewish General Hospital in Montreal, Canada. All aspects of the planned clinical trials in Canada will employ FDA standards at all levels. We estimate that it will take approximately 18 to 24 months from start to finish. Following successful completion of Phase I clinical trials, it is likely that we will be required to make Adva-27a available to patients under the “compassionate-use” guidelines.
Adva-27a Patents
US Patent Number 8,236,935 covering Adva-27a was issued on August 7, 2012. Sunshine Biopharma is the direct owner of this and all rights, title and interest in and to all worldwide patents covering Adva-27a, including all issued and pending patents under PCT/FR2007/000697 and PCT/CA2014/000029. Sunshine Biopharma has not granted any licenses or rights to any entity under these patents.
