The movement of the cells inside our bodies is a lot like a mass of people on trains during the rush hour. The cells make their way through the bloodstream carrying their genetic baggage, driven by mysterious signals that tell them where to move to and when to stop. Occasionally, they have stopover points, signs on the blood vessels' inner surface, the endothelium, where they can leave the train and settle down. There is an endless movement of cells in and out of tissue. BioKine Therapeutics Ltd. and its founder Prof. Amnon Peled specialize in the movement that controls the movement of cells.
"Cell migration is a vital process, both in normal development and disease," explains Peled. The ability to migrate plays a vital role in, for example, moving cells from the immune system to an area of damaged tissue." The wound sends signals to healing skin cells to head in its direction. If there is a germ in the wound, the signals unwittingly sent by the infection enable a white blood cell to identify it and relentlessly chase after it until it swallows it up. During a heart attack, the heart sends out signals that it has been damaged, drawing cells from the bone marrow which help it heal. Every distressed tissue sends out signals like these that tell the body how it can help. Unfortunately, cancerous cells also take advantage of this mechanism. They use all the regular cell transportation mechanisms to migrate to additional organs and create metastases.
BioKine focuses on just one of these traffic mechanisms, the one that controls cell entry and exit to and from bone marrow. This is the place where all the immune system cells and blood cells are created. "It is also where cancerous cells love to migrate to," says Peled, "because from there they can easily spread everywhere else." BioKine identified a substance contained in bone marrow called ligand which invites the cells in and binds them tightly so that they do not move, and also ties them to the place on the receptor occupied by bone marrow, preventing them from leaving. The tighter the ligand's grip is, the more difficult it is for the immune or cancerous cell to venture outside of the bone marrow.
Peled studied cell migration mechanisms in the course of his academic career, specializing in the ligands and receptors that control the entry and retention of cells in the bone marrow. He founded BioKine with the aim of making practical use of this knowledge, and the process had two possible applications. In cancer, bone marrow functions, as mentioned earlier, as a station from which cancerous cells are dispersed to other places with the goal of becoming metastases. If the ligand can be made to hold on to the cells tightly, preventing them from being released, the chances of metastasis developing will be reduced. If the cells are bonded to the receptor, it can be used to transmit signals or toxins that kill off the cancerous cells.
The second application is also related to cancer, albeit indirectly. The ligand can also hold on to stem cells which become white blood cells, and which constitute a vital part of the immune system. In cancer patients, the immune system is destroyed in order to destroy the disease, following which it is rebuilt on the basis of stem cells. The problem is that these cells take too long to regenerate and leave the bone marrow. In this case, the ligand's grip on the stem cells can be weakened, thereby causing them to be ejected into the blood system faster, so that a new, healthy immune system is created in less time.
BioKine was formed under the auspices of the Weizmann Institute of Science incubator, which has since ceased operations. It has raised $3.5 million to date, most of it from Clal Biotechnology Industries Ltd. (TASE: CBI). It has also raised finance funds from angel investor Shmuel Cabilly, Hadasit Bio Holdings Ltd. (TASE:HDST), the EU Sixth Framework for R&D, and the Chief Scientist. Amnon Peled is, as mentioned earlier, BioKine's founder and CEO, and the chairman is regulatory expert Laurence Shaw, formerly director of medical and technical affairs at Revlon Health Care Ltd., and CEO and president of Manhattan Pharmaceuticals Inc. (AMEX: MHA). The company's COO is Dr. Orli Eizenberg.
BioKine was established in 2000 and can now be said to have reached its second generation. The company's direction was based from the outset on the intervention in the molecule restraining mechanism in the bone marrow, but the initial experimentation aimed to intervene in the mechanism, using other molecules which attack the ligand itself. It was only later on that Peled came across a new molecule, discovered by Prof. Nobutaka Fujii from the Graduate School of Pharmaceutical Sciences at Kyoto University, Japan, which attacks the CXCR4 receptor which bonds with the ligand on the cells inside the bone marrow. In this manner, BioKine attacks the same mechanism but using a different approach, thereby further improving the efficacy of the drug it is developing.
The mechanism BioKine is working on has already been identified by various companies, such as Genzyme Corp. (Nasdaq: GENZ), which specializes in drugs for niche diseases. "Genzyme paid $600 million for a molecule, which is an antagonist for the same ligand that we specialize in, and which also causes the release of stem cells from bone marrow for use in transplants," says Peled. "This molecule successfully completed the third and final phase of clinical trials. Our antagonist has a slightly different form and it is far more effective in releasing these cells. It also removes different cells from those removed by Genzyme's molecule. In addition to this activity, and in contrast to the other molecule, our molecule also generates cell renewal within the bone marrow itself," he adds.
There is a possibility that, because of this, this molecule will not be used to extract cells from a donor but for another function instead - recovery by the cancer patient himself after treatment for bone marrow cancer. "The chemotherapy that Leukemia patients undergo kills the immune system and slows recovery down," explains Peled. "We cause the system to resume functioning much quicker, and this reduces the incidences of severe infection after chemotherapy." BioKine is not targeting a new market here either. A treatment designed to accelerate immune system recovery already exists, but it uses a different mechanism, which sends a signal to stem cells inside the bone marrow, speeding up the rate of their selection and conversion to white blood cells. "This product takes a day or two to speed up the renewal process, yet it still has $5 billion in sales a year," says Peled. "The beauty of it is that this process is synergetic with ours."
And that's not all. BioKine's molecule causes the release of cells by acting on the cells themselves, preventing them from bonding with the ligand inside the bone marrow. But apparently, it also bonds with leukemia cells, and not only prevents them from bonding, but also accelerates their natural death.
And there is even a syndrome that appears to have been created specially for BioKine's drug. It is a genetic syndrome where the ligand has too tight a grip on the cells, so patients suffering from it do not have any immunity. "When I heard about it I said, great! We've got a market! But then I realized that only 200 people a year contract this disease," says Peled. At any rate, BioKine's product is due to begin Phase I trials for post chemotherapy immune system rehabilitation.
Published by Globes [online], Israel business news - www.globes.co.il - on January 23, 2008
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