SUNSHINE BIOPHARMA INC ANTICANCER RESEARCH 32: 4423-4432 (2012) Adva-27a, a Novel Podophyllotoxin Derivative Found to Be Effective against Multidrug Resistant Human Cancer Cells
Excerpt… In the search for novel etoposide analogs with improved efficacy and pharmacokinetic properties, which can overcome multidrug resistance of human cancer cells, we designed and synthesized Adva-27a, a non-ester, nitrogen-containing glycoside analog of etoposide (Figure 1C). This study describes the evaluation of Adva-27a using a battery of biochemical, cell biological, and pharmacological analyses. Compared to etoposide, Adva-27a was found to be substantially more potent against two multidrug-resistant human cancer cell lines, and has a better metabolic stability and pharmacokinetic properties than etoposide. Taken together, these results suggest that further development of Adva-27a is warranted as a novel topoisomerase II inhibitor for use in human cancer therapy with multidrug-resistant tumors.
Patents Sunshine Biopharma holds the exclusive rights to Adva-27a in the United States. We received this license from Advanomics Corporation which owns the international patent applications filed on April 27, 2007 (PCT/FR2007/000697). These patent applications, which are now issued in Europe and the United States (US 8,236,935) and are still pending elsewhere around the world, were originally owned by Institut National des Sciences Appliquées de Rouen (France) and have recently been purchased by Advanomics Corporation. On January 14, 2013, Advanomics Corporation filed a new patent application covering Adva-27a manufacturing processes as well as new Adva-27a derivatives and other compositions. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=% 2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8,236,935.PN.&OS=PN/8,236,935&RS= PN/8,236,935
• Adva-27a is effective at killing different types of multidrug resistant cancer cells, including: • • Breast Cancer (MCF-7/MDR cell line) • Small Cell Lung Cancer (H69AR cell line) • Uterine Sarcoma (MES-SA/Dx5 cell line) • Pancreatic Cancer (Panc-1 cell line) • 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 1.44 micromolar. • Adva-27a has shown excellent pharmacokinetics profile as indicated by studies done in rats. • Adva-27a does not inhibit tubulin assembly.
Dr. Steve Slilaty Profile Dr. Steve N. Slilaty, age 57, was appointed as our CEO, President and Chairman of our Board of Directors on October 15, 2009. In addition, since February 2002, Dr. Slilaty has been President and Chief Scientific Officer of Advanomics Corporation, Montreal, Canada, a privately held company engaged in the research, development and commercialization of drugs for the treatment of various forms of cancer. Advanomics Corporation is the third in a line of biotechnology companies that Dr. Slilaty founded and managed through their early and mid stages of development. The first, Quantum Biotechnologies Inc. later known as Qbiogene Inc., was founded in 1991 and grew to over $60 million in annual sales. Today, Qbiogene is a member of a family of companies owned by MP Biomedicals, one of the largest international suppliers of biotechnology reagents with a catalogue containing over 55,000 products. The second company which Dr. Slilaty founded, Genomics One Corporation, now known as Alert B&C Corporation, conducted an initial public offering (IPO) of its capital stock in 1999 and, on the basis of its ownership of Dr. Slilaty's patented TrueBlue Technology, Genomics One became one of the handful of participants in the Human Genome Project. Formerly a research team leader of the Biotechnology Research Institute, a division of the National Research Council of Canada, Dr. Slilaty also served as a consultant in a management and advisory capacity for a major Canadian biotechnology company between 1995 and 1997 during which time the company completed one of the largest biotechnology IPO‘s in Canada raising over $34 million. Dr. Slilaty received his Ph.D degree from the University of Arizona in 1983 and a Bachelor of Science degree from Cornell University in 1976. In addition, Dr. Slilaty holds a position as Adjunct Professor at Universit-é du Qu-ébec in the Department of Microbiology and Biotechnology.
Garmen Laboratories will manufacture 1 kilogram of Adva-27a, Sunshine Biopharma’s flagship anticancer drug candidate in development for multidrug resistant cancers. The 1-kilogram GMP material will be used to complete the remaining studies required to file an Investigational New Drug application with the U.S. Food and Drug Administration and conduct the Breast Cancer Phase I clinical trial of Adva-27a scheduled to be hosted at McGill University’s Jewish General Hospital in Montreal, Canada. Garmen Laboratories is a U.S. Food and Drug Administration-registered facility and accredited by Health Canada. More on Garmen Labs can be found at www.garmen.ca. http://sunshinebiopharma.com/wp-content/themes/sunshinebiopharma/press/SBFM_Pres s_Release_Garmen_V2_Final.pdf
SBFM is in the process of changing its incorp from Colorado to Delaware and then to Canada. This move allows them to receive grants directly rather than through their sole parent company Advanomics. They are within a few months of filing their IND which should be a nice catalyst.
As always, do your DD.
Sunshine Biopharma, Inc.
Offer to exchange 56,839,061 Common Shares for 56,839,061 Common Shares of Sunshine Biopharma Inc., a Canadian corporation, that have been registered under the Securities Act of 1933
We have filed a registration statement on Form S-4, of which this Prospectus is a part, to register the issuance of Common Stock that is to be delivered to our shareholders by a to-be-formed Canadian corporation upon the completion of a redomestication of our Company, Sunshine Biopharma, Inc., a Colorado corporation. We are proposing to change our jurisdiction of incorporation from Colorado to Delaware, then to the Canadian federal jurisdiction under the Canada Business Corporations Act (the “CBCA”) through a process known as a continuation under Delaware and Canada corporate law (the “Continuation” or the “Continuance”). In order to give effect to the Continuation, our Board of Directors has adopted a plan of merger under the Colorado Revised Statutes (the “Plan of Merger”) to reincorporate our Company into a Delaware corporation in order to take advantage of the laws of the State of Delaware authorizing a continuation, and simultaneous therewith, to file a Certificate of Transfer with the Delaware Secretary of State to continue our existence as a Canadian corporation.