How Alpha Cancer Technologies is making chemotherapy less toxic
Note: This article originally appeared in the Canadian Business Journal.
Canadian pharmaceutical company Alpha Cancer Technologies Inc. is developing a way to deliver chemotherapy more effectively and with lower doses so the treatment does not cause toxicity in patients. If successful, the company’s drug products, which use a recombinant human alpha fetoprotein (AFP) with unique immuno-oncology properties, could revolutionize chemotherapy by targeting cancer cells instead of healthy cells and eliminate toxic effects of treatment.
As part of a larger financing, one of the largest U.S. biotechnology companies recently purchased 15 per cent equity in the company for US$ 7.5 million, providing substantial resources for future development. The company says its drug products have the potential to greatly improve cancer outcomes for the majority of suffering patients because its targeted treatment method will be more effective and safer than current therapies.
The Canadian Business Journal spoke with founder and CEO Dr. Igor Sherman and chairman Richard Potts about its innovative targeted chemotherapy delivery platform, and what puts it ahead of the competitors.
“Typically, chemotherapy works by killing cancer cells, but it also damages normal cells. That’s why there are all of these nasty side effects,” Sherman says. “So if you can eliminate the side effects and the toxicity, you can then, in theory, provide a sufficient dose to kill the cancer and cure the patient.”
What is Alpha Fetoprotein?
The AFP is a shuttle protein that transports nutrients to fast growing fetal cells. It also functions as an immune regulatory protein protecting the fetus from the mother’s immune system. Sherman explains that the protein enters cells through specific receptors found on every embryonic cell. During pregnancy, AFP is secreted into the mother’s bloodstream where it picks up (binds) nutrients required by rapidly growing fetal cells. AFP continues circulating in the bloodstream until it encounters AFP receptor on a fetal cell. It then binds this receptor and the the receptor/AFP complex with its nutrient payload are transported into the cell where AFP unloads the nutrients. AFP then exits the cell and continues the cycle shuttling nutrients from the mother to the embryo selectively.
Sherman explains that while AFP production stops after childbirth, most cancer cells similar to embryonic cells express AFP receptors. He says cancer cells, in many ways, revert to an embryonic state, with up to 80% of solid and liquid tumors expressing AFP receptors. By attaching a chemotherapy “payload” to AFP, the company can selectively deliver toxins to cancer cells because AFP can only enter the cells expressing AFP receptors and mature healthy cells do not have this receptor. This targeted delivery prevents chemotherapy from entering normal cells, which increases its effectiveness and significantly reduces toxicity.
“If you load AFP with chemotherapy instead of nutrients, it acts as a Trojan horse that enters the cancer cell, and delivers this chemotherapy selectively to these cells,” Sherman says.
The company has several promising products that include non-covalently bound chemotherapy, such as paclitaxel, thapsigargin, and chemically linked chemotherapy, such as maytansinoids. These generic chemotherapy drugs have been proven effective but are associated with significant toxicity including, bloody diarrhea, hair loss, vomiting, nausea and damage to peripheral nerves. AFP itself has been proven safe with no significant toxicity seen in over 400 patients in Phase I and II clinical studies. Only mild irritation at the injection sitewas observed in these patients. In vitro and in vivo results show that the company’s lead product ACT-901 (comprised of AFP and paclitaxel) can successfully target cancers without the “off-target” healthy cell hit and at a lower dose than conventional chemotherapy.
Cancer and Autoimmune Treatments in the Pipeline
Alpha Cancer has had multiple projects on the go since it acquired AFP rights from the U.S. company, Merrimack Pharmaceuticals. It is currently collaborating with PolyTherics Limited, a U.K. company that provides technologies and services to develop biopharmaceuticals. The collaboration is producing a range of AFP conjugates with cytotoxic payloads attached to AFP in order to target cancer cells with chemotherapy.
The company is also working on preparing a preclinical package for ovarian cancer that includes manufacturing and toxicology work. It expects to start treating patients in 2017 and apply for approval approximately three years thereafter. Because ovarian cancer is an orphan disease (i.e., relatively small number of patients are annually diagnosed in U.S. with ovarian cancer), the company can access an FDA program that allows businesses to market drugs after Phase II trial. The FDA program stipulates, however, that the company must complete Phase III trial to confirm Phase II results, or the drug will be taken off the market.
Additionally, Alpha Cancer is continuing the development path for AFP that was originally pursued by Merrimack. Sherman says the protein shows considerable promise for treating autoimmune diseases, such as myasthenia gravis. In fact, studies in Israel and the U.S. showed that AFP blocks the antibodies that attack the nerve and muscle junction (called Acetylcholine receptors), improving the symptoms of the disease. Sherman explains that because Merrimack completed several Phase I trials and a large Phase II trial, the protein can advance quickly to market by entering Phase II trial in myasthenia gravis. Sherman adds that AFP could also be useful in treating other autoimmune diseases, such as multiple sclerosis and lupus.
Business of Treating Cancer
Alpha Cancer holds exclusive worldwide rights to AFP with patents that extend to 2024. It expects to secure up to 12 years of market and data exclusivity following marketing approval in the U.S. and Europe. The company has benefitted from over $100 million that Merrimack already spent on development, including a large drug master file with the U.S. Food and Drug Administration and human safety data from over 400 patients treated in Phase I and II clinical trials. As a result, the company has a significantly mitigated risk profile in every area of development and a speedy path to market.
As a virtual company, Alpha Cancer outsources all of its projects to research institutes and contract research organizations such as the University Health Network, Ontario Cancer Institute at the Princess Margaret Cancer Centre, PolyTherics, Charles River, Southern Research Institute, etc. As a result, it doesn’t have a monthly burn rate. “We are a virtual company in the sense that we are efficiently using our cash and focusing on external support with best in class contractors,” Potts says. “It’s a really efficient model. It allows us to manage our resources well, and it provides a little bit greater comfort for our investors as well.”
The company works with some of the best medical professionals in the field. For example, Dr. Daniel D. Von Hoff, a renowned medical oncologist and oncology drug developer who has conducted national clinical trials with more than 200 new antineoplastic and biologic agents, approached the company and offered to be its principal investigator for upcoming clinical trials. Potts says Dr. Von Hoff called the company’s cancer treatment method the most rational approach to treating cancer he has seen in a long time.
Canada Lags Behind in Life Science Investments
Alpha Cancer’s targeted cancer treatments seem destined for success, but biopharmaceutical companies in Canada face many obstacles. Canada has one of the richest and most robust scientific communities in the world, but Potts says the Canadian government and institutional investors have not invested enough time and money in the industry. “If you take the market value of all the TSX-listed mining companies in Canada, basically they would match the market valuation of just two biotechnology companies in the United States,” Potts explains. “If you take four biotechnology companies in the United States that didn’t exist 25 years ago, the market value of those companies, now, is bigger than all the big six Canadian banks as well as ManuLife and Sun Life combined.”
“It’s extremely frustrating for anyone who has been in the industry for any length of time. It’s an area that is deserving of attention and institutional funding and it’s an area that can clearly reward investors very well,” Potts says. “There are opportunities for huge returns, as well as great opportunities for Canada to lead in this knowledge-based industry.”