Israel flexes its bio-med muscles

Scientists develop new monthly contraceptive and artificial knee ligaments replacement.

By ZVI HELLMAN
artificial ligament 521 (photo credit: TAVOR MEDICAL SOLU TIONS)
artificial ligament 521
(photo credit: TAVOR MEDICAL SOLU TIONS)
An Orthodox Jewish woman from Beit Shemesh says the time has come for a new method of contraception. Rachel Teitelbaum, an American immigrant with a PhD in microbiology and immunology, has developed a new contraceptive for women that does not interfere with their hormonal balance and needs to be used just once a month.
Hervana, the new contraceptive developed by Teitelbaum, was runner-up at the Israel Life Sciences Industry’s BioMed 2012 conference in May. She says it could be an alternative to the pill, currently used by more than 100 million women each day in a market worth $8 billion that is growing at a rate of 19 percent each year.
“There are many bad side effects from using hormonal-based contraceptives,” Teitelbaum tells The Jerusalem Report.
“While they satisfy an important need, it’s been 50 years – it’s time for something new.” Risks associated with the pill include increased risk of blood clots, breast and cervical cancer and birth defects.
Teitelbaum has developed a non-hormonal alternative to the pill that makes use of antisperm antibodies, which prevent conception by inhibiting sperm motility. The idea is not new. Anti-sperm antibodies have been the basis for proposed “contraceptive vaccines.”
But contraceptive vaccines have never lived up to their promise. There was no efficient way to stop the production of the antibodies in case a woman chose to become pregnant.
Hervana solves this problem by providing a local antibody production agent, instead of having a woman’s body produce the antibodies. Teitelbaum has developed a method by which lactobacilli, which are rodshaped bacteria, have been engineered to express anti-sperm agents.
The idea of introducing bacteria into the body instead of hormones might at first thought seem unappealing, but Teitelbaum is quick to point out that lactobacilli are naturally present in healthy premenopausal women. They promote resistance to pathogenic micro-organisms and promote the integrity of the female genital tract. Hervana simply introduces a naturally healthy bacterium that in addition is harnessed to work as a contraceptive. It can also reduce the likelihood of contracting an STD .
“Women are encouraged to eat yoghurt – the reason is because of the bacteria lactobacillus that is in yoghurt and is healthy for the reproductive tract.”
Teitelbaum says the new method has several advantages.
“It does not influence hormonal balances and avoids the bad side effects from using hormonal-based contraceptives,” she says. “It provides protection for long durations of time and promotes resistance to STD infection.
The delivery method will presumably be any kind of vaginal formulation, suppository, cream or foam, which would require only a once a month application, for each cycle.
If women want to become pregnant the following month there would be no reason to hesitate.”
Hervana is currently in a pre-clinical phase. The effective use of its lactobacillus for contraception has been proven to work in mice. Teitelbaum is seeking investment and strategic partnerships with pharmaceutical companies with the aim of starting human clinical trials within the next 18 months. Her company was recently awarded a grant by the Bill and Melinda Gates Foundation.
Teitelbaum grew up in New York City and completed her doctoral studies at Albert Einstein College of Medicine before moving to Israel 13 years ago. She initially worked as a patent agent in Israel, but says she missed the laboratory bench.
‘I can do that’
“I kept seeing all these other great inventors moving along with their ideas and I said, ‘Hey, I can do that.’ I came up with this idea and started pushing it forward,” she says.
Teitelbaum believes that what she is doing is important for women’s health around the world. “Let’s face it, there is such an enormous problem in the developing world, where there is no access to contraception and women are using abortion as a method of contraception. Two hundred and fifteen million women in the developing world do not have access to contraception, and about 50 million out of 190 million pregnant women per year undergo abortions because they could not obtain contraceptives. I care about my community and many other communities,” she says.
But she also concedes that there is a certain incongruity in an Orthodox woman living in the strictly Orthodox community of Ramat Beit Shemesh being involved in founding a start-up devoted to contraception. “Well, if some of the people there knew what I was doing!...” admits Teitelbaum.
David Zakai, Hervana’s chief operating officer and vice president, points out that birth control is common among women in many religious communities, including ultra- Orthodox.
“Not just used, it is sanctioned in certain situations. There is no reason to assume that there will be any rabbinic objection,” says Zakai.
The first prize at BioMed 2012 went to Tavor Medical Solutions, a four-year old company based in Ashkelon. To demonstrate what Tavor produces, Jonathan Yahalom, the company’s clinical affairs manager, reaches into a bag and pulls out a long, thin greencolored object that looks like a tube made out of a soft and flexible densely braided net. This, he says, is an artificial ligament prosthesis called Knee-T-Nol.
“The anterior cruciate ligament (ACL) is one of the key factors stabilizing your knee joints,” says Yahalom. “Hyperextensions and twists of the knee may cause it to tear or even totally rupture. Eighty percent of all tendon and ligament tears are in the ACL. What we are offering is a simple solution to a very painful problem.”
Many patients who seek orthopaedic treatment for ACL tears are young and highly physically active, including athletes and soldiers. Women are three times more prone to ACL ruptures than men. Most people who suffer an ACL tear are directed to corrective surgery. Non-surgical physiotherapy often fails to produce full functional stability and leaves patients susceptible to meniscus tears.
About 400,000 surgical procedures for correcting ACL ruptures are performed annually in the United States, with another 300,000 in Europe. With the average ACL surgery costing $3,500 in the United States and $2,500 in Europe, the market potential is on the order of $1.9 billion.
However, surgical reconstruction has welldocumented drawbacks. It usually involves grafting ligaments from another source in place of the torn ACL. But donor grafts from other individuals are difficult to obtain and include a risk of disease transmissions.
Grafting a ligament taken from another part of the patient’s body avoids these difficulties, but it leaves scarring at a weakened donor site, is an invasive procedure and requires an extended recovery time.
Implantation
“Instead of taking another ligament from another part of the body, you can just take our prosthetic ligament and implant it using the same procedure as in the normal ligament implantation procedure,” says Yahalom.
“Drill two holes, insert it, and that’s it. It is a simple solution to a painful problem.”
Tavor was established in 2008 by two brothers, Nir and Idan Tobis. Nir is a businessman who was the CEO of a commercial sports chain, and Idan is a mechanical engineer with extensive experience in medical device development.
“The two brothers had a friend in common who suffered a torn ACL,” explains Yahalom. “Seeing what he went through led them to the idea behind Tavor.”
Tavor is not the first company to come up with the idea of creating an artificial prosthesis for replacing anterior cruciate ligaments.
Several polymer-based prostheses have been tried and tested. None, to date, have managed to obtain full unconditional regulatory approval for use in ACL reconstruction.
Tavor believes that its Knee-T-Nol can succeed where the others have failed. That confidence is based on the material that is used in Knee-T-Nol: an alloy of nickel and titanium called nitinol, which exhibits superelasticity that makes it very springlike.
The nitinol elasticity gives Knee-T-Nol mechanical properties that resemble those of a natural tendon, tolerating strains while exerting the right amount of force for knee stability. Tavor has filed three patent applications for its invention.
The pre-clinical trials of Knee-T-Nol included both in vitro (test tube) and in vivo (live) tests. The in vitro tests focused on the mechanical behavior of the product, especially getting the tensile and elastic properties to desired levels and ensuring that the material does not corrode. The in vivo tests on lab animals tested for safety, bio-compatibility and smooth integration into living tissue. Tests were also conducted on inserting the prosthesis into cadavers, to test its efficacy and to prove feasibility of anchoring it properly to human bones.
Clinical trials have been underway at the Shaare Zedek Medical Center in Jerusalem since March 2011. Fourteen surgical procedures implanting Knee-T-Nol have been conducted to date. While two of the procedures failed, patients from the successful operations began walking again without knee braces in less than four days, compared to at least seven days for autografts.
Rehabilitation time was cut from a minimum of six months to just four.
Reducing procedure time by nearly 50 percent is cost-effective with regards to operating theater resources, physician time and patient bills. Faster rehabilitation time is attractive to patients and employers. “Imagine an athlete missing only half a season instead of a full season,” says Yahalom. “The reduced pain and quick return to normal activity are very important.”
Israel has a small but innovative biomedical sector. There are about 1,000 life science companies operating here, with 50 to 60 new companies established every year.
The worldwide bio-medical end-market is characterized by a small number of giant firms, such as Medtronic, Johnson & Johnson, Kendall/Tyco and St. Jude Medical. Most successful start-up exits are accomplished via acquisition by larger companies, not through an initial public offering. This trend fits the Israeli technology sector well, since most local companies plan on an acquisition exit strategy, concentrating on innovative research and development with less emphasis on marketing and distribution.
The same disruptive factors that are driving technological innovation in general are being felt keenly in the bio-medical field. Computerization, miniaturization and an endless supply of discoveries in material sciences spawning novel bio-materials are enabling the creation of new medical advances that seemed out of reach only a few years ago. In fact, industry leaders are now saying that medical innovation companies are outpacing both their customer base and regulators in the speed at which they come up with new ideas.
For the medical market, an industry that is tightly regulated and in which cautious, time-consuming clinical trials have traditionally been necessary requirements for taking forward steps, it will not be easy or uncontroversial to adopt the technological disruptions and dislocations that have become commonplace in the telecommunications and computer industries.
None of these considerations, however, are holding back Israeli bio-med start-ups.