TEL AVIV – Israel's 10th annual biomed conference drew a crowd of 6,000 attendees from more than 60 countries. Since its founding, this conference has drawn larger audiences each succeeding year. Israel is home to more than 900 life science companies with 50-60 new startups added each year. About 41% of all life science companies operating in Israel today were established during the past 5 years. These companies attract hundreds of millions of dollars in investment capital from venture capital firms, public offerings and from the world's major healthcare corporations. Israel is rich in new ideas and fosters entrepreneurship. It ranks as the highest country in patents per capita in areas such as medical devices, diagnostic kits, cancer therapy and drug delivery.
Sara Toth Stub, a reporter for the Wall Street Journal, wrote that the “appetite for Israeli public offerings of life-science companies is booming.“ There were four IPOs for life science companies on the Tel Aviv Stock Exchange (TASE) in the first three months of 2011 and several more were planned for the first half of this year. She noted that there are about 1,000 life science companies in Israel and that there is strong collaboration between academia, the military and the marketplace.
Startups target the Tel Aviv stock exchange for listing
Eitan Akiva is Senior Vice President at Clal Finance & Underwriting (Tel Aviv), Israel's leading brokerage in the life science sector which raised 30 billion shekels ($8.6 billion) in 2010. It is a holding company of the IDB Group (Tel Aviv), Israel's largest conglomerate. Akiva observed that several European and American companies are in the process of submitting to TASE draft prospectuses for IPOs. He said that “TASE is a step before NASDAQ and it is growing and getting more professional with the addition of analysts.“ Factors that have contributed to the boom in IPOs are the diminished availability of venture capital funding and looser TASE guidelines for research and development companies in recent years. This has enabled dozens of one-product companies that lack regulatory approval to raise money and be listed on the exchange. According to Yaakov Michlin, president/CEO of Yissum Technology Transfer, a spinoff of the Hebrew University (both in Jerusalem), the listings have brought more public attention and helped attract seed capital for startups.
There are a proliferation of medical device companies that are housed within Israel's many incubator groups and their technologies cover the full spectrum of medical specialties, as is reflected in the profiles of companies profiled below with offerings in orthopedics/spine, gastroenterology, neurology, nephrology, urology, gynecology, dermatology/aesthetics, and surgery.
Devices for orthopedic and spinal surgery
Tavor (Ashkelon) is developing KNEE-T-NOL, a ligament prosthesis made from braided and super-elastic Nitinol for use in anterior cruciate ligament (ACL) reconstructive arthroscopic surgery. This product offers a safe and effective off-the-shelf alternative to biologic tendons harvested from the patient (autograft) or from a cadaver (allograft). The use of a Nitinol alloy prevents the phenomena of fatigue, creep and leeching which are associated with earlier-generation polymer-based solutions. The implant is attached at the femoral and tibial ends using standard fixation devices such as cortical buttons, cross pins or screws. The artificial Nitinol graft is expected to offer a shorter rehabilitation period since it uses a smaller width bone tunnel for implantation and it provides the required mechanical strength from day one. A 12-patient pilot clinical study was recently initiated in Israel and an additional 12-patient study is planned in Europe.
LRS Ortho (Katzrin) is developing a device for improved accuracy in the drilling and cutting of bone. Its Universal Guiding for Orthopedic (U-GO) system is a platform technology that enables orthopedic surgeons in locating the drilling/cutting point, then aim and drill accurately. The device provides a simple and accurate way of placing distal fixation screws into the holes of IM nails. Its L-RaySpot system solves the distal end aiming problem using a laser-based opto-mechanical aiming device and computerized image processing in getting correct alignment for the drilling and placing of bone screws through the bone and into the holes of an IM nail. The company has completed a 30- patient clinical trial in Israel and Russia. LRS recently received 510(k) clearance from the FDA and is seeking a distributor in the US. LRS Ortho is developing products for spinal and pelvic fractures which use 3-D imaging software, a laser and imaging process and an automated instrument for building a 3-D model of the spine.
Ortho-Space (Lod) has developed the InSpace biodegradable balloon for use in treating shoulder rotator cuff injury in patients with non-reparable tendon tears. The balloon is made from polylactic acid and caprolactone. It can be implanted between the acromion and humeral head by an arthroscopic or mini-open procedure and resorbs in about one year. An alternative treatment is the major procedure of shoulder joint replacement surgery. The company has completed a clinical trial on 150 patients in Israel and Slovenia which includes a 3-year follow up on 24 patients. Additional trials are planned on 200 patients in France and Italy. The balloon implant will be sold at a price of $2,000 per unit. Validation sales are currently being made in Israel and Europe. Rotator cuff syndrome is the 3rd most common orthopedic pathology after knee and back cases.
PolyPid (Ness Ziona) is developing a biodegradable carrier, based on the fusion between polymers and lipid-based delivery systems, enabling prolonged and controlled drug release from weeks to months in accordance with a pre-programmed dosage rate. The company's current research efforts are focused on the local treatment of a bone infection. Its initial application is for the treatment of contaminated open fractures. Its first product is BonyPid, a biodegradable bone void filler that is micro-coated with a PolyPid biodegradable formulation. The coating gradually releases the selected antibiotic over a period of 3-4 weeks needed to overcome an acute or chronic bacterial infection. Following the release of the drug, the bone void filler maintains its role as a scaffold for new bone formation. The company plans to begin a 100-patient clinical trial by the end of this year.
FacetMed (Ashkelon) has developed the DualAxis pedicle screw system for the treatment of a degenerative spine. It is a non-rigid, multi-axial spinal fixation system for posterior stabilization and fixation of thoracic, lumbar and sacral regions. Non-rigidity in the screw reduces stress tenfold at the bone-screw interface and improves load transfer between vertebrae. It is expected to reduce the surgical failure rate and the need for secondary procedures. This system offers a new approach for use with the aging population that suffers from low bone quality with resulting fixation problems. The company plans to make a 510(k) submission to the FDA and projects market introduction in 12 months in the U.S.
Products used in GI surgery
Cologuard (Jerusalem) is developing an elastic sheath for protecting the anastomosis from leaking following colorectal surgery. Leakage is estimated to occur in 10% of gastrointestinal surgeries. The Cologuard device is positioned at the anastomosis site and creates an intraluminal bypass for colon contents. Fixation of the sheath to the colon wall is achieved using a simple mechanical element which accommodates the colon's anatomical characteristics. After 10-14 days, when the risk of anastomotic leak is eliminated, the Cologuard can be removed easily without surgical intervention. Cologuard has completed initial preclinical tests as part of the proof of concept stage.
LifeBond (Caesarea) is also pursuing a treatment to prevent leaks at the anastomosis site with its LifeSeal GI, a sealant that is applied to the staple or suture line for added reinforcement. The company anticipates receipt of the CE Mark with market introduction in Europe next year. LifeBond is also developing LifePatch, a dry surgical hemostat. LifeBond has recently raised $20 million from venture investors, bringing its total capital raised to date to $30 million.
Ocure (Jerusalem) is developing a sterile, semi-adherent wound dressing for treating anal fissures. The dressing is an open cell polyurethane foam that is wrapped with a semi-occlusive wound dressing. It maintains a moist physiological environment at the fissure lesion to accelerate epithelialization, wound healing and to relieve local pain. An applicator is used for device insertion. The product is intended to relax the anal canal and thereby break the cycle of spasms and pain which cause the stoppage of blood flow. The absence of a blood supply leads to anal fissures. It is estimated that over two million people in the U.S. suffer from anal fissures. Ocure has conducted an initial 10-patient clinical trial in Israel and recorded measurements on a pain scale and documented any occurrence of anal spasm. The company plans to expand clinical trials in Israel and Europe and is seeking a potential partner to market its product.
Currently, conservative therapy for anal fissures includes a high-fiber diet, stool softeners, analgesic creams and warm baths, but healing takes about two months with a high rate of disease recurrence. Surgical sphincterotomy is a last treatment option. It is 95% effective in healing anal fissures but can result in asymmetry of the anal canal and irreversible anal sphincter damage which may cause fecal incontinence.
Neurological implant and pain control device
PerflowMedical (Tel Aviv) is developing a temporary endovascular device that establishes immediate perfusion of the ischemic brain. The device is self-expandable, easily deployed and captured across the occluding thrombus. It uses the patient's blood pressure to perfuse through an internal bypass. The concept of the device is to “let the brain breathe“ and preserve the ischemic penumbra, thus minimizing tissue irreversible damage and improving the prognosis for patients suffering from ischemic stroke. The company has conducted a preclinical study on pigs and plans to pursue a 510(k) filing with the FDA. Perflow's solution for treating ischemic stroke is faster than the existing products that require a 2-hour procedure which are the Merci pigtail device from Concentric Medical (Mountain View, California) and the Penumbra aspiration device from Penumbra (Alameda, California.
Good Energies (Haifa) exhibited its B-Cure Laser, a handheld soft-laser device for the treatment of pain. This battery-powered device operates on the principle that the 808 nm near infrared soft laser penetrates soft tissue and biostimulates the body's natural healing mechanisms on a cellular and systemic level. It is used primarily for treating back and knee pain. It has the CE mark and is currently being sold to hospitals and pain clinics in Europe and Israel. The company is waiting for FDA clearance of its 510(k) submission.
Breaking and extracting kidney stones
Lithotech Medical (Tel Aviv) manufactures kidney stone entrapment and extraction devices that are based on superelastic Nitinol. The woven baskets have an asymmetric shape along their central axis to prevent stones from falling during extraction and to ensure easy stone capture The company's Lithotripter employs a new technology for stone shuttering and crushing. It is based on a high voltage electric pulse of nanosecond duration. This allows for breaking the stone using a relatively low energy level of under 0.5 joule. The Lithotriper is being used in 80 hospitals in Russia and expansion into China and India is planned. The company expects to soon receive the CE mark for Europe but is not planning to enter the U.S.
Treatments for SUI and pelvic organ prolapse
ConTiPi (Caesarea) has developed a non-invasive and disposable device for treating stress urinary incontinence and pelvic organ prolapse. An applicator is used for vaginal insertion and the insert is removed by pulling on a string. The incontinence device employs soft silicone splayed prongs that are compressed prior to insertion and expand to support the urethra after insertion into the vagina. While in the vagina, it serves as a sling that provides support under the urethra and thereby functions similarly to the tension-free vaginal tape (TVT) procedure for stress urinary incontinence. The device has been tested in many women in Israel, the U.S. and England and received market clearance from the FDA in 2006. It is currently a prescription device and the company is working towards receiving OTC authorization.
ConTiPi's other device, intended for the conservative management of pelvic organ prolapse, is inserted into the vagina in the same manner, and removed by the user herself by a pull of the string. While in the vagina the device lifts up all prolapsed organs. It is a disposable device which is inserted and removed by the user at her home environment. It is currently at an advance stage of clinical trials.
Aesthetic implant and equipment
Metamorefix (Rehovot) is developing a dermal implant comprised of a non-crosslinked hyaluronic acid/fibrin scaffold for aesthetic applications. The company's process produces a flowing and room temperature stable fibrin that is more functional in cell binding than a fibrin clot. It is considered to be an improvement over existing hyaluronic acid-based dermal fillers, by providing better granulation quality and less scarring. A first-in-man study in Europe has been initiated. Results from wound healing studies in pigs suggest that the company's biomaterial can potentially be used for treating acute and chronic wounds
Sonnetica (Omer) is developing a patented ultrasound-based technology for the non-invasive treatment of cellulite and varicose veins, and for skin tightening. The technology allows for the creation of microbubbles at a desired site. The microbubbles function as targeted contrast agents for localized ultrasonic absorption when exposed to relatively low power and low frequency acoustic energy. The stimulation leads to very localized and effective tissue damage, through either mechanical (cavitation) or thermal interaction. Its great selectivity results in reduced pain and side effects.
Futuristic robotic surgery
Microbot Medical (Nesher) was established in late 2010 with a vision of transforming minimally invasive surgery with two of its pioneering micro-invasive technologies that provide the accuracy of robots and automated instruments, and enable physicians in targeting the disease site with high precision.
The ViRob platform is an autonomous advancing micro-robot, and the TipCat is a platform of disposable, flexible, self-propelled, see-and-treat endoscope/catheter. The ViRob is based on a less than a 1 mm length micro-robot that is operated by an external electromagnetic field to advance forward or backward within a cavity or lumen, such as veins or arteries. The first commercial application being pursued is for a self-cleaning shunt that is implanted for the treatment of hydrocephalus which occurs in 1 out of 500 births and in about 400,000 adults (also known as NPH) in the U.S. The company is finalizing its in vitro testing and plans on entering a clinical study in the next 12 months as part of its submission for regulatory approval in the U.S. and Europe.
The TipCat platform is comprised of a series of interconnected balloons that provide forward and backward motion while allowing for a working channel to be available during the surgical procedure. Its physiologically adapted self-propelling mechanism and flexibility allows for the navigation of an endoscope/catheter over difficult anatomical structures and can potentially be used for cardiovascular, ENT, urological and gynecological procedures.
Microbot was founded by Professor Moshe Shoham, Harel Gadot, a formal global director at Johnson & Johnson (New Brunswick, New Jersey) and Shizim (Rosh Ha-Ayin), a leading life science group in Israel. Both the ViRob and TipCat were developed by Professor Shoham at the Technion-Israel Institute of Technology, where he is the director of the Robotic Laboratory (Haifa), and licensed to Microbot. He also had invented the SpineAssist robotic tool used for back surgery which is marketed in the U.S., Europe and Israel by Mazor Robotics (Caesarea). Professor Shoham envisions that the micro-robot can be used for multiple medical applications such as diagnostics and drug delivery. He is also working on a small robot that can navigate through the amniotic fluid to diagnose fetal abnormalities and help perform in utero surgery. For some applications, the ViRob would remain in place such as for brachytherapy.
Professor Alon Tal, also at the Technion, is developing the “snake“ robot for endoscopic heart surgery. It can be maneuvered around organs for better control and vision during laparoscopic procedures.