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 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-tumor 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 reduce to 1.44 micromolar as a result of resolving the two isomeric forms of Adva-27a).
  • Adva-27a has shown excellent pharmacokinetics profile as indicated by studies done in rats.
  • Adva-27a does not inhibit tubulin assembly.
Inhibition of Multidrug Resistant Breast Cancer Cells by Adva-27a Compared to the Commonly Used Drug Etoposide

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 and multidrug resistant breast cancer for which there are currently little or no treatment options available. In June 2011, we concluded an agreement with McGill University’s Jewish General Hospital in Montreal, Canada to conduct Phase I clinical trials for these two indications. All aspects of the planned clinical trials in Canada will employ FDA standards at all levels. We estimate that it will take approximately 18 months to complete Phase I clinical trials. 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 direct owner of this as well as all right, 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.

Adva-27a Molecule in 3D