State of Virginia woos Israeli life science companies
By Jerrin Zumberg October 18, 2007

An Israeli treatment that may help cure over 30 types of cancer is likely to see the light of day much quicker - thanks in part to a small group of businessman, state officials and bioscience management professionals based in Richmond, Virginia. The technology developed by startup BioCancell is just one of the many Israeli innovations that the group hopes to bring to their city.

Representatives from the group - comprising the Virginia Israel Advisory Board, a branch office of Virginia Governor Tim Kaine, the Virginia Israel Biosciences Commercialization Center (VIBSCC), the Virginia Biosciences Development Center, a life sciences research park in Richmond hosting 60 private companies, a university medical center and clinical hospital - were in Israel last week to promote their latest initiative, 'Gateway America,' aimed at luring Israeli companies developing unprecedented solutions to treating ailments and terminal diseases to the US market.

"Israel needs to move away from thinking that opportunities in the US are only in California, New York, and the major coastal cities," said Ralph Robbins, executive director of the Virginia Israel Advisory Board, referring to the lack of attention Israeli companies pay to less familiar US cities.

With the support of his boss Kaine, the year-old Gateway America program was launched to bolster the state's stake in Israeli developments in the life sciences.

"Israeli technologies are recognized around the world for their innovation, advanced development, and functionality, and Virginia is proud to continue its expansion into the biosciences field with a leading international partner," Kaine said in an official statement about the program.

That statement is backed up by statistics released by the Israel Ministry of Industry, Trade and Labor, which shows that Israeli researchers lead the world in the number of life science patents issued per capita. There are almost 900 Israeli companies in various stages of development working on life science industry-related products.

The 'Gateway America' representatives were in Israel to choose a limited number of program participants from the country's packed field of life science companies, in addition to cultivating their first Virginia-Israel partnership with BioCancell. The companies chosen for the program will be regularly counseled and invited to attend a December conference at the Development Center in Richmond where they will be offered business counseling, exposure to major US medical distributors and investors, hospital access to carry out clinical trials, funding, and marketing strategy sessions.

Committee member and VIBSCC executive director, Donna Edmonds, confirmed they had narrowed the field to 300 Israeli companies with products in an advanced enough stage of development to be considered for the program, but met with only 30 on this trip.

"In my more than 35 years as a professional in the health management and medical distribution field, I've never seen so many interesting close to market, simple and elegant solutions," Edmonds told ISRAEL21c after three days of interviews.

Products pitched to the committee included improved drug delivery mechanisms, advancements in laparoscopic surgery, and a wide array of platform drugs, or drugs applicable to a range of diseases, including cancer.

Both VIBSCC and the Virginia Biosciences Development Center that will host the new companies do not expect the Israelis to transfer development to the US, but rather to establish branches there for product expansion.

"The Israeli market isn't big enough for companies to be successful. Israeli companies have to go to Europe or the US to expand their products," said another committee member and the Development Center's executive director, David Lohr.

BioCancell is among VIBSCC's first clients. The Jerusalem-based biopharmaceutical corporation has patented all use of a single human gene for research purposes. The tumor enabling gene, called H19, was discovered by Hebrew University professor Avraham Hochberg 19 years ago and is expressed in more than two dozen types of cancer.

The discovery led to BioCancell's incorporation in 2004 and the company is now among the world leaders in utilizing plasmids, or self-replicating DNA molecules to treat cancer patients.

The company's research team discovered a way to identify if H19 is expressed in a cancer patient's cells and essentially turn the gene off by injecting its product, a plasmid called BC-819. The plasmid is only activated by cells that express H19, therefore does not harm healthy cells or other body systems. The key innovation of the drug is that only the cancerous tissue is destroyed without the side effects typically experienced by cancer patients undergoing intense chemical therapies where healthy tissue is affected as well.

BioCancell is now completing clinical trials concentrated on bladder cancer in Israel and readying to launch trials in the US. VIBSCC and the Development Center's management will facilitate the company's ability to conduct these US clinical trials, which pending Federal Drug Administration approval will lead to additional assistance in their eventual US marketing strategy and distribution.

"The key advantage to working with US specialists in the life sciences and VIBSCC is their knowledge of the American market," said BioCancell's director of strategic alliances, Ran Vigdor. The small company needs the contacts and manpower capable of pushing a product into the US market, which is where the appealing packaged deal of the Gateway Program steps in.

The goal of VIBSCC is to seek out companies like BioCancell and offer them entry into the US market via opportunities in Virginia.

Finding qualified companies won't be a problem according to members of the visiting Gateway America Committee.

"The huge challenge is choosing from the quality of all the companies we saw and to sort them to only three to five," concluded Lohr.

 

A veteran Jerusalem scientist hopes that his discovery will end up as a blockbuster drug for eliminating malignancy - without side effects

At a time of his life when most men would be content sitting back and enjoying retirement, Avraham Hochberg has taken on a major challenge. It's not that the emeritus professor of molecular biology doesn't have things to occupy his time. He paints, as attested by the half-dozen canvases that line the walls of his small office at the Hebrew University of Jerusalem; he plays the piano and he dabbles in genetics, including his participation in an Israeli group that includes an Israeli musicologist, a geneticist and a computer expert, which is investigating the connection between musical talent and heredity in the J.S. Bach clan. He's also studied archaeology, and once, in his younger days, guided Israeli tours to ancient sites in Turkey.

But Hochberg, now 67, has also become an entrepreneur, in the hope that something he learned at his regular job as a scientist will turn into a major cancer treatment: He is founder and chief scientific officer of BioCancell, a two-year-old company developing what Hochberg sees as a "magic bullet" to treat cancers of the bladder, the liver, the prostate - and perhaps more down the line.

BioCancell's technology is based on Hochberg's discovery, about 19 years ago, of the properties of a gene known as H19. What's unique about H19, he says, is that it expresses itself in human fetal cells and in cancerous cells, but not in the cells of ordinary, healthy people.

"Every human gene has an operating program, called a promoter," Hochberg explains in his resonant voice, as he compares the promoter to a common off-on switch. "Many genes are permanently 'on' in daily life, and there are also genes that work in an 'off-on' situation. So, for example, the gene that controls the digestive system is always 'on,' and when you eat sugar the insulin gene is on, but turns off when the level of sugar in the blood declines. For H19, the operating system is on in the fetus, off in the mature person, and on in certain cancer cells."

Hochberg and his colleagues at BioCancell utilize this special property of H19 - whose apparent function is to help tumor cells survive in the body - to develop a therapy that targets directly, and only, cancer cells. "If I take this promoter, a bit of DNA, and attach a poison to it, I could not inject it in a fetus, where the gene is in the 'on' position," he explains. "And if I give it to a healthy person, nothing will happen, because it's 'off.' But directly injected, this combination of the promoter and the toxin will kill cancer cells."

The toxin of choice is diphtheria, a deadly disease on its own. "All of Western civilization is inoculated against diphtheria, in the triple vaccination given to small children. That means that if after killing the cancer cells the diphtheria escapes, people are protected," Hochberg says. This kind of specific attack targeted directly on cancer cells, he adds, is likely to avoid most of the unwanted, often deleterious side effects present in current chemotherapy treatments, which attack a much broader range of cells in the body.

Beyond that, Hochberg developed a quick, easy and inexpensive test for the presence of H19 in cancerous tissue; H19 is found, according to the company, in about 80 percent of all bladder cancers. That means that every treatment is personalized. Hochberg emphasizes that every cancer is different, and if H19 isn't found in a particular tumor, the patient can't be treated.

Only recently, the company got approval from the U.S. Food and Drug Administ-ration, the world's most prestigious regulatory authority whose final OK is a must for any commercial medication or treatment, to begin Phase I clinical trials on humans with bladder cancer. This process happened quickly after the treatment registered a significant success with what Hochberg calls a compassionate patient. He pulls up a chart with some pictures of cancer cells, and speaks with what is clearly a great deal of pride. "Here is a man of 57 years, who over five years underwent 10 operations - that's one every six months. He had every conventional treatment, from BCG [Bacillus Calmette-Guerin, a solution inserted by catheter into the bladder] to mitomycin [a chemotherapy agent]. Everything." Hochberg points to another photo that's hard for the layman to comprehend. "His bladder capacity decreased from half a liter to 130 cc. There was nothing else conventional medicine could offer him."

In the last couple of years, this Israeli patient has received 30 treatments with the BioCancell preparation. And now, Hochberg says, "There's no sign of the cancer. He operates in a perfectly normal way."

Use of drugs under development, Hochberg notes, is not a commonplace occurrence, and it can't be done with every patient. But in some cases of last resort, when the patient, his lawyers and the hospital all agree, the Israeli Health Ministry will approve giving an experimental drug to a patient, Hochberg says, "fairly quickly, because there is nothing else to do. You have to demonstrate that available medicine can't help the patient. In pancreatic cancer, for example, you would know that there is not a lot of time, so that perhaps a direct injection into the pancreas would save the patient, or at least give him some more time. And in bladder cancer," he says, raising his voice, "what do you risk? In conventional treatment, you are going to have to remove the bladder anyway."

Compassionate treatment, though, is not part of the approval process. For that, the BioCancell bladder-cancer treatment is now undergoing formal clinical trials, at two Israeli hospitals, Meir in Kfar Saba and Wolfson in Holon. Still to come: Phase II and Phase III clinical trials, a process that is both highly expensive and time-consuming. Hochberg says his treatment could be on the market within about four years, with a little bit of luck.

The firm recently raised $3 million in a private placement to fund the trials, and hopes to put together another $8 million, possibly in an initial public stock offering on the Tel Aviv Stock Exchange. But that will get them only part of the way through the bladder cancer trials and the approval process, which usually cost a minimum of several hundred million dollars.

Hochberg makes no secret of his goal, which is selling out to one of the so-called Big Pharmas, the drug industry's giants, who have the huge sums of money and the scientific resources to develop one of the "blockbusters" that is every budding pharmaceutical developer's dream - a drug that brings in $1 billion a year in sales. The potential is there: According to 2003 American Cancer Society Figures, many thousands of people in the U.S. alone are diagnosed each year with cancers that could express H19: 57,000 for cancer of the bladder, 17,000 for liver, 30,700 for pancreas. In all, Hochberg adds, there are signs that H19 is present in 33 separate strains of cancers.

So far, he says, two big drug companies have had a looksee at his technology, but he's not ready to sell quite yet. Better, from both his point of view and that of a potential purchaser, is to carry the technology as far forward as possible, at least into Phase II clinical trials, by which time there should be positive proof that the drug is not toxic to humans. If things work out, that would both maximize the proceeds from selling to BioCancell's owners (35 percent belongs to Yissum, the Hebrew University's company for developing and selling technologies developed by its staff, 29 percent to Hochberg himself, and the rest to private investors) and minimize the risk, and the expense, to a pharmaceutical company.

Taking the money now is simply not an option. "Yissum and the other investors would never let me," he says, confiding that the Israeli investors who put $100,000 or $200,000 each into the project are not there to sell quickly.

"A good friend who invested $200,000 said to me: 'I lose more on nonsense. This time I want to give sick people a chance. If the treatment doesn't work, I won't die from the loss.'" And, adds Hochberg, "if he turns $200,000 into $400,000 it also won't make a lot of difference. What he'd like, of course, is to make a really big profit - though he's not one of those people who puts some money into the stock market and then checks every day to see if his shares have gone up or come down a few points."

In the meantime, the company is moving ahead with the development of the H19 remedy on other cancers. Hochberg notes that they've been able to kill at least part of a very large liver tumor, and says they're working on adapting their method of drug delivery, direct injection, to reach pancreatic tumors as well.

In the pipeline are two other drugs, to compliment the H19 approach. "If one cell in a cancer that does not have the H19 remains, it can later turn into active cancer after the treatment," he says. "So we are preparing a similar therapy based on another gene, called IGP2, that presents itself when H19 is not present. You need something to kill the cancer cells that don't have H19," he says. Though he hasn't seen this yet in a patient, he says he has to be ready. "It's like chess, you have to think several moves ahead."

All this seems like a very big ambition for a small company that's only two years old, has no revenues and only eight regular employees in its office and lab. But Avraham Hochberg thinks he's on the inside track to finding a major cancer cure. And if it doesn't work, there's always his painting, his music or his archaeology.

(Copyright (c) 2006. The Jerusalem Report)

BioCancell to start human drug trials - Globes Business Arena, March 2006

The company raised $3 million from private investors a month ago and needs $6-9 million more to complete the research.

Gali Weinreb 21 Mar 06

Sources inform ''Globes'' that BioCancell Therapeutics Ltd. (BioCancell) is set begin clinical trials on humans, as part of the first stage towards securing approval from the US Food and Drug Administration (FDA) for its oncology treatment. The company is reported to have raised $3 million in financing from private investors a month ago.

BioCancell was founded by Professor Avraham Hochberg, of the Hebrew University of Jerusalem (Israel) and the technology was licensed from Yissum Technology Transfer Company of the Hebrew University of Jerusalem.

Hochberg's laboratory team discovered a gene called H-19 which is the first oncofetal gene ever discovered that is present at high levels in human cancer tissues, while existing at a nearly undetectable level in the surrounding normal tissues but present in 33 different types of tumor cell. Hochberg told "Globes", "BioCancell has developed a DNA-based drug that enters the cancer cell and creates the toxin diphtheria. There will be no problem if the toxin is released into the body since the entire population is immunized against it by way of the "triple jab."

Is your drug similar to other drugs currently under development, which detect unique receptors on cancerous growths and channel various toxins through them?

Hochberg: "Our drug belongs to the class of drugs in which a gene sequence occurs in tumor cells only, thereby driving the expression of the diphtheria toxin. Our development has the potential to be adapted for use in 33 different types of cancer and we therefore think it is unique. Our first trials have focused on indications of bladder and liver cancer.

"The H-19 gene can also be used to identify cancerous cells. Our drug is unique in that it can differentiate by way of single cell sensitivity analysis, between healthy and cancerous cells, while other methods of diagnosis analyze tissue texture, which needs 9-10 cells to determine whether or not the tissue is malignant."

What were the results of your preliminary trials?

"We saw a patient with cancer of the bladder who had been given up as a lost cause by the medical community. We have managed to keep this patient's bladder clean of growths with our drug for four years.

"In cancer, we do not conduct clinical trials on healthy participants, but begin testing directly on cancer patients, a stage we call IIa. We then move on to more extensive trials, known as stage IIb. We are looking to recruit 15 more patients for our trials."

How long will the current funding last and much more will you need to continue the process?

"Our funding will be enough to proceed with stage IIa and we will need an additional complete stage IIb, which will encompass both the current application in treatment of bladder cancer and other conditions in the future."

BioCancell chairman Avi Barak added, "A group of US investors is looking at the possibility of investing in us, and we have also been contacted by two underwriters on the Tel Aviv Stock Exchange (TASE) who have offered to float us here in Israel. We are currently considering both offers."