Turbocharge a drug with a secret sauce, use less of it to make it work safer, faster, and more efficiently, partner with big companies to limit your own costs, and develop the drug offshore, cutting a 10-year development timeline in half. That plan would delight any biotech, and this young biotech has an extra advantage — that the person in charge is, metaphorically, an old China hand, Abe Abuchowski.
Abuchowski, 60, grew up on a chicken farm in Vineland and was an early pioneer on the biotech scene. In fact, his company, Enzon, was among the first to go public in the state, and the first in New Jersey to get drugs on the market. Abuchowski also jumpstarted New Jersey’s first organization for biotechs, now called BioNJ, and was its first president. He left Enzon 13 years ago when it turned away from the original technology. “PEGylation was the core technology that gave birth to that company,” he says. He took about a decade to “smell the flowers.”
But eight years ago, from a home office, he started the research for another firm, Prolong Pharmaceuticals, using the very same PEGylation method to attach a polymer to a protein-based drug to come up with a slightly different drug. As one of the first chefs to brew PEGylation sauces, he has kept both his credibility and his contacts. “I spent many years pulling together all the information I needed. The raw material supplies are not easily obtainable,” says the president of Prolong in a telephone interview.
Abuchowski’s firm appears small — just seven people, but he partners with larger companies, so size doesn’t matter. At Harold Kent’s high tech park, Princeton Corporate Plaza, he has 3,500 square feet of lab space, “wet labs, hoods, clean areas, everything we need, and when the time comes to expand, we can. Harold has been very good to us and startups don’t need the Taj Mahal.” Abuchowski expects to have products on the U.S. market in two or three years.
About $7 million has been invested in Prolong, most of it from Manhattan-based KBL Healthcare Ventures. KBL’s Zachary Berk is the chairman and CEO of Prolong. Prolong has spent $6 million in three and a half years and has a burn rate of about $130,000 per month. It expects to be profitable by 2012. With a new $1,125,000 grant from the NIH in his pocket, and even in this uncertain economic climate, Berk has set out to raise an additional $15 million.
PEGylation was the subject of Abuchowski’s thesis, working with the now retired Frank Davis at Rutgers in 1971. PEGylation is the only FDA approved drug delivery system for proteins, and it made possible eight of the products that are available today, says Abuchowski. Since the time PEGylation products were approved, they have sold a total of $25 billion, $8 billion of developed by Abuchowski.
What does PEGylation do? It attaches polyethylene glycol (PEG), to a protein molecule. So coated, the molecule does not pass through the kidneys and therefore is not siphoned out of the body. PEGylated products help the drug companies retain their rights to drugs with patents that have expired because they are somewhat different from those drugs. In fact, they are better than the original drugs — they stay in the body longer, requiring fewer doses, and are cheaper to manufacture, because they require less of the protein raw material.
Abuchowski believes Prolong Pharmaceuticals has almost unlimited growth possibilities. Two of its products — Peg-EPO and Peg-GCSF (both based on original drugs made by Amgen) — have a combined market of $14 billion dollars. “Taking even a small share of that market is a huge number for us,” he says. “These drugs are off patent globally, and will soon go off patent in the United States. For a big company like J&J, it may be small, but for Prolong, this opportunity is beyond belief. For our other product, the oxygen therapeutic market is desperate for it, and it is larger opportunity, perhaps $20 billion. This market is waiting for a product, and we want to be the pioneers here.”
PEG-EPO is a version of erythropoietin, sometimes called Procrit, which stimulates red blood cell production to treat anemia, particularly for dialysis patients. Zydus Cadila, based in India, has licensed the technology and will invest $15 to $20 million to bring it to market. Zydus has the rights for PEG-EPO in India, but Prolong has the United States rights.
PEG-GCSF stimulates white blood cells. It will compete with a drug made by Amgen to prevent infection in cancer patients who have received high doses of radiation.
PEG-Hemoglobin has three potential therapies so far.
The first is AfterShock, for trauma and hypovalemic shock, useful for combat wounds and for loss of blood in childbirth. It can also be used in cases of criminal assault and auto accidents, which, combined, are the number one cause of death in civilians under 35 years of age. AfterShock received the newest grant, for $1,125,000 in October, from the National Institutes of Health’s national Heart, Lung, and Blood Institute (NIH/NHLB) and it may soon get another one.
Sanguinate is for anemia. The NIH/NHLB put its imprimatur on this product by awarding $850,000 to pay Prolong to produce the hemoglobin product for research labs.
Hemozyne is intended for stroke, traumatic brain injury, myocardial infarction, and sickle cell disease. It is being tested at three universities.
Other potential products on Prolong’s radar screen are PEG-uricase, for the treatment of hyperuricemia due to gout or following chemotherapy; PEG-arginase for treatment of melanoma and Hepatocellular carcinoma; PEG-peptide antibiotic to treat Staphylococcus infections; and PEG-streptokinase for myocardial infarcts.
As for competition in the PEGylation field, Enzon has three original products from the Abuchowski regime. Another competitor is Nektar, a Massachusetts-based firm, which has developed products for Roche, Amgen, and Pfizer. “There is plenty of room for a lot of people,” says Abuchowski. “Whatever their brains can develop, they can do.”
Abuchowski’s motto is “a company doesn’t exist to do research, but to get products on the market.” He finds ready partners for this motto in Asia, where venture capital is scarce, and quick-to-market products are the norm. In Asia it is also easier to find eligible “naive” patients available for clinical trials. (Naive patients are those who have not been taking other drugs that disqualify them from a trial.)
India-based trials and manufacturing methods generally adhere to the standards of the U.S. Food and Drug Administration — and they are considerably cheaper. That’s because biotech is in its infancy in India and China, says Abuchowski, yet those countries benefit from 20 years of United States knowledge. Their scientists have been educated in the United States and have returned home to start their own companies. “They are building modern facilities and developing biogeneric products for their populations,” he says. “Pretty much everybody agrees that this is the next economic boom.”
“When I started Prolong, my idea was to first go out to those markets,” says Abuchowski. “Plus, we had willing companies. We will license the products to those markets first. They give us money. They are required to take the product through clinical trials and do the manufacturing, and we buy the material in its final form.”
Asian scientists have had little experience with PEGylation, and Prolong offers the necessary support. “It saves us an enormous amount not to have to build and validate a facility. Then, with an immense amount of clinical data, we will get faster approval in the United States. We are making money while we are making money.”
The first such partnership was signed with Zydus Cadila, a 9,000-worker global firm with headquarters in India, and an outpost at 210 Carnegie Center
Another avenue for “making money while making money” is to produce raw materials for other research labs to use. The NIH/NHLB grant for Sanguinate falls into this category. “Instead of spending money to test our product, we get to sell it to the research community while we are working on it,” says Abuchowski.
“Once Abe puts his mind to something, it will get done, and it will be successful,” says Cliff Mintz of BioJobBlogger. A resident of East Windsor, Mintz has a consulting firm, BioInsights, and is a sweat-equity investor in Prolong (see sidebar, page 39). “Abe is a wealthy man who was able to do what most other CEOs were unable to do, even with more resources and more capital.
Mintz notes that Abuchowski has an egalitarian view, that he can convince the lab technician with the most menial job that he is the most valuable person in the laboratory, yet he can hang out with the board chairman and negotiate a fair agreement. “He is a very savvy business guy with moxie,” says Mintz. “But most people who know him in his home town don’t know him as anything more than as a guy who raises chickens.”
Abuchowski will not confirm how much money he got when he walked away from Enzon, though it was probably in the single digit millions. He says only: “I live very well.” This good life includes a 17-acre farm in Lebanon, where he keep chickens, along with ducks and dogs.
While he was a stay-at-home dad for nine years, Abuchowski continued his avocations. He is a pilot and looks forward to the time when he can once more have another company plane (he had one for Enzon, which he used like a car). Woodworking is one of his hobbies — he built most of the furniture in his home — and he works on antique cars. His wife, an immunologist, used to be on the staff at the Liberty Science Museum and now works at Rutgers. They have a son in his last year at Rutgers’ Cook College and a daughter who is a senior in high school.
Abuchowski grew up in rural Vineland, where his parents were chicken farmers. “The chicken industry in South Jersey died in the 1960s with the huge mechanical chicken farms. We were raising 5,000 chickens versus 100,000 to 1 million chickens.” To this day, he won’t eat eggs from a grocery store.
The farm went bankrupt, and his parents went into buying houses, renovating them, and renting them out. His mother had the business smarts, he says, and the family built a profitable real estate business that his sister now runs in Vineland. As he learned construction, working alongside his father, he also learned that “integrity and honesty were the most important things in life.”
He worked his way through Rutgers, from which he graduated in 1970, by climbing up the McDonald’s chain, starting as a cleaner and ending up as a manager. “I learned how to make money, manage people, and do quality control. Whether you are doing quality control on a hamburger or a molecule, the procedures are the same.”
Martial arts, he says, has also turned out to be a valuable business asset. “Tae Kwon Do taught me to truly focus all my energies on a task and not let ancillary things interfere.” Add scientific expertise to these two experiences, he says, “and you have an entrepreneur. I learned on the job at Enzon and learned pretty well.”
Frank Davis assigned Abuchowski, his PhD student, to work on PEGylation. Davis had patented a method for attaching the polymer onto a protein, and had proved that this could reduce immunogenicity and improve circulating life. Abuchowski found the missing piece: an attachment with bovine serum albumin.
Abuchowski and Davis founded Enzon in 1982 and grew it into a fully-integrated company. It went public almost immediately.
First Abuchowski targeted two diseases that other companies had ignored because the markets were so small. Just eight years later the first product, Adagen, was on the market. Developed as an “orphan drug,” on a fast track status, Adagen helped alleviate a rare severe immunodeficiency disorder known as the “bubble boy syndrome.” The next drug, Oncaspar, approved in 1994, was for a disease almost as rare — acute lymphoblastic leukemia in children.
Biotech was so new then that in 1990 Enzon was only the fifth biotech company in the nation to take a drug to market, yet Abuchowski had lots of opposition, even from within the firm.
Meanwhile he started on a third product, PEG-Intron, an alpha-interferon therapy for hepatitis C. By the time it was approved in 2001 Abuchowski had left the firm, followed by succession of executives who turned away from PEGylation technology and acquired lots of debt. The current CEO, Jeff Buchalter, arrived in 2004 and, according to the firm’s website, has re-financed the debt and plans to sell off the biotech assets. “He was able to restore shareholder confidence and stabilize Enzon’s stock price,” writes Mintz on his blog. “Unfortunately his effort may not be enough to save the company from acquisition or merger.”
As a protein chemist who developed the first company that took the process from research to completion, Abuchowski says he has a better understanding of all the important issues than almost anyone. “It is an art and a science. I am the scientific leader from beginning to end. I have the entire process in mind from beginning to end.”
One of Prolong’s three current products, PEG-EPO substitute, ran into controversy recently. It was being used for chemotherapy patients, but accumulated statistics showed that fortifying red blood cells can also accelerate tumor growth. “They didn’t know that four years ago,” says Abuchowski. Back then cancer patients with severe anemia were given aggressive treatment. “They went to too high a level of hemoglobin,” says Abuchowski, noting that oncologists are more cautious now. “We are learning.”
He also learned his lesson about how to grow and keep control over a company, and now that the biotech industry has 25 years of experience under its belt, he has lots more options. “Enzon went public six months after opening its doors. I wish I could have done it differently. I would have gone through a number of private rounds. It is a little too early to talk about Prolong going public.”
Prolong Pharmaceuticals, 7 Deer Park Drive, Suite F, Monmouth Junction 08852; 732-438-1133; fax, 732-438-1138. Abraham Abuchowski, CEO. www.prolongpharmaceuticals.com.