Taking a drug from idea to an actual treatment takes many years of research and costs hundreds of millions of dollars.
For every drug that wins approval from the Food and Drug Administration, thousands of experimental compounds fail in testing to prove safe and effective, or never even make it that far
Researchers on that journey from lab to bedside at Williamsville-based For-Robin Inc. hope their work will lead to a new therapy for breast cancer and other tumors. Success could be lucrative, too.
It's a long slog, but the University at Buffalo spinoff recently received a crucial boost from the National Cancer Institute, which selected the company to join its experimental therapeutics program to help accelerate promising treatments into clinical trials in humans.
"It's exciting because this gets us where we want to be," said Kate Rittenhouse-Olson, president and chief science officer. "We competed against big and small companies, and only 10 percent or fewer are selected."
The National Cancer Institute funds a lot of research, but this program is not directly about funding. Instead, it's seen as a partnership to speed up a cancer drug's path from discovery through development.
Among other things, the institute will produce enough of For-Robin's drug for use in safety testing in animals and humans, and file an investigatory new drug application with the FDA, a precursor to human clinical trials. Rittenhouse-Olson estimated it would have cost For-Robin $4 million to accomplish this on its own.
That's a huge lift considering the odds against success.
Only about 14 percent of all drugs in clinical trials eventually win approval from the FDA, according to an MIT study published earlier this in the journal Biostatistics. That's much higher than previously thought. However, the approval rates can vary widely based on the condition the drug is designed to treat, ranging from a high of 33.4 percent for vaccines for infectious diseases to only 3.4 percent for investigational cancer treatments.
For-Robin was established in 2012, but its roots go back much farther and are personal.
Rittenhouse-Olson is an immunologist by training who has spent more than 25 years studying a certain antigen – foreign substances in the body that provoke the immune system to respond.
In this case, the antigen of her focus – the Thomsen-Friedenreich antigen, named after its discoverers – is essentially two connected sugar molecules that remain hidden in normal tissue but come to the surface of tumor cells. This antigen assists cancer cells in metastasizing, or spreading, to new parts of the body.
She and her colleagues created in the lab an antigen's enemy – an antibody engineered to block and then kill the tumor. It's called JAA-F11, a combination of the initials of her children – Jennifer, Anna and Andrew – and the grid location on the culture plate where the lab-created antibody first grew in 1994 after cloning a mouse spleen cell with a mouse tumor cell.
The endeavor to turn JAA-F111 into a safe and effective drug for humans has been inspired by the woman for whom the company is named, Robin Quataert, Rittenhouse-Olson's older sister, who died of breast cancer at age 31 in 1986.
The News talked to Rittenhouse-Olson about her work.
Q: When do you expect to begin a clinical trial?
A: Maybe in two years. We'll now look for pharmaceutical partners or venture capital or grant funding to do this in that time frame.
The data for JAAQ-F11 looks great, and I believe we will get there. But we need to do the trials. This is a drug that is not quite ready for prime time.
Q: How does JAA-F11 work?
A: An antigen is just a protein, and proteins have carbohydrates on their surface. JAA-F11 works by blocking the activity of this carbohydrate – two types of sugar molecules basically – found on tumor cells. This is the Thomsen-Friedenreich antigen we're looking at. Our antibody only binds to this antigen when it is on the tumor cell, reacting both chemically and biologically.
When I started my research into this, I wasn't thinking of a treatment. I wanted to make a vaccine. People have a little of this antibody in them. The question we asked ourselves is could we make more of it if people already had a little?
We eventually used the antibody in mice in which we had grafted human tumor cells, and saw that the antibody blocked the tumor from spreading in the mice.
Q: How effective is the antibody?
A: People already have a little of this antibody in them. Our work so far shows that if we give more of it, the antibody blocks tumors from spreading. It's important to note that the work has been in human tumors grafted into mice. We need to test this in humans, and that is what the clinical trials will do.
We tested JAA-F11 on 1,269 cancerous tissues from lung, prostate, colon, bladder, colon and breast cancer, including the aggressive triple-negative form of the disease (the form from which her sister likely died). It reacted in about 85 percent of the specimens, and it only binds to the antigen when it is on the tumor cell, and not normal tissue.
Q: How else might JAA-F11 be used in cancer treatment?
A: The antibody can be radiolabeled (a radioactive susbtance is attached) to diagnose cancer. We are looking at a way to use it to direct a person's white blood cells to kill the tumor. You could also attach a chemical to kill the tumor, and not just stop it from spreading. If you are trying to interest companies, the ability to directly kill the tumor is what they are interested in, not just blocking its growth.
Q: What do we know about the safety of JAA-F11?
A: The antibody doesn't bind with normal human tissue, and people already have a little of it. That shows me we shouldn't be hurting someone if we give them more.
Q: Is there a patent yet on this experimental therapy?
A: We expect to be granted a patent within a month (as of early May) from the U.S. patent office, which has issued a notice saying we will be allowed a patent. This is very important because it starts the (patent protection) clock again for companies that might want to invest in clinical trials, something that's probably going to cost something like $200 million, maybe more. Companies want to know that they will have plenty of time to do trials and get a return on their investment.
Q: What's a key lesson you have learned along the way?
A: I didn't know how to be a entrepreneur, but Buffalo has been amazing in helping me learn. So many people and organizations have helped us – UB helped with the patent and has supported us for years, Hauptman-Woodward (Medical Research Institute) did the crystallography to help us understand what part of the mouse antibody was binding to the antigen.
Buffalo has been full of people willing to help us. I tell people to come here. Don't expect anything to happen in a minute. Keep plugging away. Look for what you need to prove to companies to show you have a good product. It takes perseverance and sometimes stubbornness. You have to believe in yourself and your product.