By James Netterwald, Ph. D.
Pancreatic cancer drugs are making a comeback thanks to a new platform and new attitude.
A physician walks into an examining room where a patient is waiting to receive news about a possible diagnosis of cancer. “I’m sorry to say you have pancreatic cancer,” the physician says. “You may have only six months to live.”
A diagnosis of pancreatic cancer is an absolute death sentence with more than 36,000 deaths per year in the United States. With such a high fatality rate, pancreatic cancer is a devastating disease that is desperately in need of better therapy. Prior to November 2010, the main treatment drug for pancreatic cancer was Gemzar (Eli Lilly), but now that drug is available in generic versions by a few different companies such as APP Pharmaceuticals, Hospira, and Sandoz.
Actually, Gemzar going off patent set up an interesting business model for other pharmaceutical companies as Lilly’s sales of Gemzar, almost all for pancreatic cancer, are approximately $1.4 billion annually. There is a huge opportunity for a more effective drug, but pancreatic cancer presents a huge challenge for companies new to the therapeutic area for two major reasons. First, a large proportion of patients may die before the company can see a therapeutic effect of the drug. Second, from a business perspective, the high mortality rate does not lend itself to long-term sales of the drug, thus pancreatic cancer does not have the highest return on investment. For these reasons, few pharmaceutical companies, nowadays, attempt to develop drugs for pancreatic cancer.
One pharmaceutical company courageous enough to resurrect pancreatic cancer drug research is CureFAKtor Pharmaceuticals in Buffalo, NY. In an interview with Life Science Leader magazine, CureFAKtor executives gave an insider’s view of how the company is applying its powerful drug discovery platform to develop novel drugs against pancreatic cancer and various other cancers. Using its drug development platform, CureFAKtor is bringing forward not one drug, but several. According to Shep Wild, president and CEO of CureFAKtor, his company’s drugs target a very fundamental mechanism in many human cancers, which is the basis for its platform and presents the company with a valuable business opportunity.
William Cance, MD, a surgeon and chief of surgical oncology at Roswell Park Cancer Institute in Buffalo, NY, serves as chief scientific officer of CureFAKtor. He explains that the company has a very broad target with broad indications that was used to develop a platform technology containing several different novel cancer drugs. In terms of its business model, he says, CureFAKtor has three competitive advantages. The first of those advantages is the drug target — focal adhesion kinase (FAK) — is found in almost all solid tumors. FAK functions as a survival signal, building a force field around the tumors. CureFAKtor’s portfolio of drugs is developed to try to remove that force field from several areas. The second competitive advantage is that there are abnormal levels of FAK in almost every solid tumor: breast, pancreas, colon, melanoma, lung, liver, brain, ovary, sarcoma, and more. Finally, CureFAKtor’s approach to attacking cancer cells differs from that traditionally done by the pharmaceutical industry. The company’s platform inhibits tumor function by disrupting protein-protein interactions instead of using the traditional approach of inhibiting protein kinases, an approach that often leads to off-target (side) effects of the drug. CureFAKtor’s 40 different drugs target different sensitive sites and disrupt the protein-protein interactions that would normally occur at those sites. CureFAKtor’s ultimate goal is to use its platform to make all of these drugs adaptable to personalized medicine. The company says that each of its 40 different drugs will attack one factor in a patient’s cancer signature.
Funding From Grants And More
Fifteen million dollars of the funding for CureFAKtor has come from, and will continue to come from, grants awarded by the United States National Institutes of Health (NIH). NIH funding started when Dr. Cance was a researcher at the University of Florida, and the funding will continue until 2015. CureFAKtor also has pursued angel investment over time and received funding from high net worth individuals, families, and trusts. Its other investors are the Roswell Park Cancer Institute and the University of Florida Research Foundation in Gainesville, FL. “Angel investors have seen what the company has to offer, including the startling results of the preclinical work, and they have come to see what’s behind it,” says Wild. “The investors see that FAK is in every solid tumor, and our platform has startling results in almost every tumor we test. What they believe is that this is a major breakthrough in the treatment of cancer.” Additionally, Wild’s personal connections, from his past life as an investment banker, have invested in CureFAKtor.
Wild says the company will be looking for business partners in the future, and that its business strategy is not to be a pharmaceutical company in the classic sense. Many of the drugs produced by large pharma companies are off patent, and big pharma pipelines have been dry for a number of years, so larger companies are looking to smaller pharmaceutical companies for innovation. One of the companies providing this type of innovation is CureFAKtor. Says Wild, “Big pharma does a wonderful job of manufacturing, distributing, and selling drugs, so we don’t need to do that. What they don’t seem to be very strong at is coming forward with new innovative compounds. So, we have a lot of drugs in the pipeline, and we expect to be licensing them.” CureFAKtor’s technology seems to be generating a good deal of interest, and the company has already been approached by large pharma companies based both in the United States and overseas, who may become potential partners.
Advantage Of Orphan Drug Status, Clinical Trials
The FDA granted CureFAKtor Pharmaceuticals orphan drug status for its drug CFAK-C4, which is indicated for pancreatic cancer. “Our very strong preclinical data with our drug alone, and in combination with gemcitabine, led the FDA to give us orphan drug status,” says Cance. CureFAKtor presented its preclinical data in January 2011 at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium. The data demonstrated that CFAK-C4 reduced tumor growth in vivo in mouse pancreatic cancer cells by up to 60%. CFAK-C4 combined with chemotherapy drug gemcitabine had a synergistic effect that yielded an 80% reduction in pancreatic cancer tumor size. This data also found that CFAK-C4 combined with gemcitabine had a prolonged effect on pancreatic tumor growth. Two weeks after treatment, the tumor size in the previously treated group was approximately 75% smaller than the tumor in the control group.
“Pancreatic cancer is a very tough mountain to climb. In fact, it was said in one scientific paper that drug companies go to pancreatic cancer to die, something that we do not expect to do,” says Cance. The reason for such a strong statement is that most of the drugs indicated to treat pancreatic cancer are not efficacious. “Right now we have very strong efficacy in preclinical pancreatic cancer models. Our mechanism of action is that the drug disrupts the ability for pancreatic cancer cells to make new blood vessels and opens pathways that allow the chemotherapy to be more effective,” says Dr. Cance.
The company plans to apply for IND (investigational new drug) status for CFAK-C4, and then eventually put the drug through clinical trials. However, CureFAKtor does not plan to bring the drug to market alone. Instead, the company plans to license the drug to a larger pharmaceutical company which will eventually manufacture and market the drug. “We have a number of advisers helping us find the right partners and determining when we should license,” says Wild.
CFAK-C4 is now moving toward Phase 1 clinical trials. However, CureFAKtor’s strategy is to trial the drug in not just pancreatic cancer, but in other cancers as well, such as breast cancer and melanoma where the company has already demonstrated very strong preclinical results.
Another strength of CureFAKtor’s business model is that the company can complete clinical trials of its pancreatic cancer drug quickly, which will cost less than trials for other cancer drugs. “In clinical trials of pancreatic models, it does not take long to measure efficacy because half of the people die within six months after diagnosis. So, trials would be shorter in comparison to other trials. And, this makes it less expensive to run trials,” said Wild.
Pancreatic cancer is a devastating disease that currently has extremely limited treatment options, thus presenting both a challenge and an opportunity for pharmaceutical companies courageous enough to enter the field. CureFAKtor Pharmaceuticals is hitting the floor running by employing a powerful platform for developing effective new drugs for pancreatic cancer and other cancers.