BBI Contributing Editor

BOSTON, Massachusetts ā€” Techvest's 4th annual Healthcare Conference, held here in October, hosted 145 presenting companies, of which 58 were private businesses. The conference expanded upon its prior focus on tissue repair, replacement and regeneration with the addition of specialty pharmaceutical and drug delivery companies. An objective repeated by many of the biosurgical product companies was to develop an implanted device having controlled release of a drug or other biological agent, which undoubtedly stems from the anticipated commercial success of drug-eluting coronary stents.

Further evidence of this initiative is the recent announcement by Medtronic Vascular (Santa Rosa, California), a division of Medtronic (Minneapolis, Minnesota) to explore the use of inhibitors of multiple proteases and cytokines, obtained from CollaGenex (Newtown, Pennsylvania), in combination with medical devices. Similar development programs are planned by Angiotech Pharmaceuticals (Vancouver, British Columbia), which is in the process of acquiring Cohesion Technologies (Palo Alto, California), a maker of biosurgical products.

MacroPore Biosurgery (San Diego, California) is developing bioresorbable polymer implants made from polylactic acid for fixation, stabilization or fusion of the spine, as well as for treating diseases, deformities or trauma of the musculoskeletal system. These implants are intended to replace allografts. It manufactures products for spinal and reconstructive surgery that are sold by Medtronic Sofamor Danek (Memphis, Tennessee) under a strategic global partnership. These products include the OS Spine System for providing containment and protection in bone grafting procedures; OS Orthopedic System, which serves as a protective covering for the reconstruction of donor site defects; and Hydrosorb Shield, a bioresorbable film for temporary wound support and soft-tissue reinforcement. The company has also developed and markets directly in the U.S. its Surgi-Wrap reconstruction film for soft tissue support and for preventing postsurgical adhesions in specific ENT procedures. The Surgi-Wrap adhesion barrier film received the CE mark last May for the prevention of postsurgical adhesions in general, cardiothoracic, spinal and obstetric surgeries. In October, MacroPore Biosurgery acquired StemSource (Thousand Oaks, California), a supplier of adult stem cells derived from adipose tissue, in order to expand its platform technology to include stem cells for regenerative therapies.

OsteoBiologics (San Antonio, Texas) is developing bioabsorbable polyglycolic/polylactic acid porous scaffolds for the repair and replacement of articular cartilage and bone. These include Immix CB, a multiphase cartilage/bone scaffold which is awaiting FDA authorization to begin clinical trials, and Immix Extender, a bone graft scaffold for supporting the in-growth of new bone or for the addition to marrow, blood and bone chips at a fracture site as an extender of graft materials. The Immix Extender is currently in preclinical trials to support a 510(k) submission. Clearance for dental applications was received in May. The company also has developed Actaeon, a hand-held instrument that measures articular cartilage stiffness for determining the degree and scope of cartilage degeneration. The current market size for cartilage repair is $575 million, based on 770,000 annual procedures, and is estimated to reach $1 billion by 2005.

Genzyme Biosurgery (Cambridge, Massachusetts) is developing expanded applications for its leading biosurgical products which include Synvisc, a viscoelastic material for treating osteoarthritis of the knee, a line of Sepra products for postsurgical adhesion prevention, Carticel for repairing articular knee cartilage and FocalSeal-L, a sealant for preventing air leaks in cardiothoracic surgery. In addition, the company is undertaking long-range cell therapy and gene therapy development programs. It will conduct, in collaboration with Myosix (Paris), a 300-patient Phase II trial in Europe using autologous cell therapy for slowing the progression from a heart attack to heart failure and for repairing damaged heart muscle. Data are being evaluated from a 28-patient Phase I trial using hypoxia-inducible factor-1 (HIF-1 a) to induce blood vessel growth (angiogenic gene therapy) to treat advanced peripheral artery disease. An additional trial will be conducted to assess the use of HIF-1 as an adjunct to coronary artery bypass surgery. Genzyme Biosurgery also has research programs for the controlled release of drugs from implanted devices including the treatment of post-operative pain from a Sepra product and a drug for preventing atrial fibrillation to be incorporated in FocalSeal CV, a sealant under development for use in cardiovascular surgery.

BioMimetic Pharmaceuticals (Franklin, Tennessee) is completing a pivotal trial for a combination of a recombinant human platelet-derived growth factor (rhPDGF-BB) with a resorbable synthetic bone matrix ( -tricalcium phosphate) for periodontal regeneration and for the treatment of cranio-maxillofacial bone defects. The product is projected to be sold in Europe in late 2003 and a year later in the U.S. The company is exploring applications of its technology for use in orthopedic fractures. Periodontal and orthopedic applications of the growth factor were licensed from ZymoGenetics (Seattle, Washington) and it is manufactured by Chiron (Emeryville, California). Orthovita (Malvern, Pennsylvania) supplies the bone matrix, which has FDA clearance.

OraPharma (Warminster, Pennsylvania) is in the preclinical development of osteopontin (OC-1016), a bone-regenerating compound that is intended for use as a coating on dental implants. It may also have application as a bone putty for regenerating bone lost from periodontal disease as well as for sinus and bridge augmentation. The company, which at the time of the Techvest conference had been seeking a dental implant company as a strategic partner and planned to outlicense 0C-1016 for orthopedic applications, now is in the process of being acquired by Johnson & Johnson (New Brunswick, New Jersey). OraPharma's leading marketed product is Arestin, a drug for treating periodontal disease. Currently, 14 million patients in the U.S. are being treated for periodontal disease.

Dentigenix (Kirkland, Washington) is focused on the development of biologically based dental therapies, using tissue engineering, growth factors and pluripotent cells. The company is in animal trials with a proprietary biomimetic tissue-inducing scaffolding for dentin and whole tooth regeneration with the aim of replacing many endodontic (root canal) procedures. About 2.5 million root canal procedures are performed annually in the U.S. Early research is also being conducted on dentin/enamel junction and salivary gland regeneration. Partners are sought for all of these development programs.

Polymerix (Piscataway, New Jersey) is developing a new class of pharmacologically active biodegradable polymers, called PolymerDrugs, that incorporate drug molecules as the major component of the polymer backbone for sustained drug delivery. PolymerDrugs can be formed into microspheres for injection, inhalation or oral therapy or applied as coatings on medical implants for sustained drug release. Polymerix is developing PolyAspirin polymers that are prepared from two parts salicylic acid and one part dicarboxylic acid linker such as sebacic acid. The degradation rate of PolyAspirin can be reduced by using a derivative of salicylic acid or by using different linkage molecules. PolyAspirin erodes to generate salicylic acid that was shown in animal studies to impart an anti-inflammatory effect. The initial focus is directed at the use of PolyAspirin as a coating on implanted medical devices such as stents, meshes, orthopedic and dental implants.

OrthoLogic (Tempe, Arizona) markets OL1000, an electrical stimulation device for healing nonunion fractures, SpinaLogic, an external device used as an adjunct to lumbar spinal fusion surgery, and the OrthoFrame/Mayo Wrist for external fixation. The company plans to enter the orthobiologics market with Chrysalin, a synthetic 23-amino acid peptide that corresponds to a portion of the naturally occurring human thrombin molecule and can be produced at one-10th the cost of bone morphogenic protein. Chrysalin stimulates the body's own natural healing process which results in accelerated tissue repair without affecting the blood clotting activity of naturally occurring thrombin. Chrysalin was shown in preclinical trials to double the rate of fracture healing with a single injection into the fracture site. In July, OrthoLogic received authorization from the FDA to begin a pivotal Phase III trial that is expected to include 500 patients at 25 to 30 centers in the U.S. Animal studies were conducted using Chrysalin microparticles in a cartilage defect model and it was shown to stimulate articular cartilage repair. A wide range of orthopedic applications is envisioned for Chrysalin including accelerated healing of fresh fractures, surgical fractures and spinal fractures as well as cartilage, tendon and ligament repair.

OrthoLogic has an exclusive license from Chrysalis BioTechnology (Galveston, Texas) for orthopedic applications of Chrysalin. Chrysalis BioTechnology is focusing on the use of Chrysalin for soft tissue repair and has partnered with the Ross Laboratories division (North Chicago, Illinois) of Abbott Laboratories (Abbott Park, Illinois) for the development of Chrysalin for treating diabetic ulcers and other dermal wound applications. The company is also studying the potential for using Chrysalin to revascularize ischemic heart tissue.

LifeCell (Branchburg, New Jersey) produces four human tissue-based products. The company directly markets AlloDerm for plastic reconstructive and burn procedures and Cymetra for the correction of soft tissue defects. AlloDerm also is sold by BioHorizons (South Birmingham, Alabama), a dental implants company, for periodontal applications. Repliform, used for urology and gynecology procedures, is distributed by Boston Scientific (Natick, Massachusetts) and Graft Jacket is sold by Wright Medical Technology (Memphis, Tennessee) for orthopedic applications. The company's proprietary tissue matrix technology is used to remove cells from allograft tissue without damaging its biochemical and structural components. This results in a non-cellular matrix that acts as a template for normal tissue regeneration. LifeCell is applying its tissue matrix technology to vascular, nerve and orthopedic repair. It also is investigating the use of human tissues as carriers for therapeutics.

Modex Therapeutics (Lausanne, Switzerland) was granted by the FDA humanitarian use device designation for EpiDex, an autologous skin product for treating chronic wounds. EpiDex is a human skin equivalent derived from adult stem and precursor cells found in the patient's hair follicle. Clinical data have shown that an artificially cultured epidermal product grown from hair can be superior to the transplantation of the patient's own hair. The company recently reported that it would merge with IsoTis (Bilthoven, the Netherlands).

Protein Polymer Technologies (San Diego, California) genetically engineers biomaterials composed of high molecular weight proteins that are processed into products having specific physical and biological properties. They include urethral bulking agents for treating stress incontinence, dermal augmentation products for cosmetic and reconstructive surgery, surgical adhesives and sealants for repair of spinal discs, scaffolds for wound healing, and depots for local drug delivery. Clinical trials are under way for incontinence and dermal correction products that are based on silk-elastin block copolymers. These polymers have segments encoding the crystalline structure of silk combined with segments encoding the elastin component of mammalian elastin, thus providing both strength and flexibility. The polymers are injectable liquids that transition after injection into pliable hydrogels. The company is conducting preclinical tests of an injectable nucleus replacement for repair of spinal discs for treating lower back pain.

BioSyntech (Montreal, Quebec) is exploring the use of its BST-Gel, an injectable and biodegradable liquid that solidifies into a hydrogel at body temperature, for the local delivery of drugs. BST-Gel is prepared from chitosan, a natural biopolymer that is found in abundance in the shells of crustaceans, e.g., shrimp and crabs. BioSyntech has collaborative programs with hospitals in Montreal for researching the use of BST-Gel as a vehicle for delivering paclitaxel for treating breast cancer and camptothecin for treating ovarian and prostate cancers. The company also is working with Novartis (Basel, Switzerland) to develop an ophthalmic drug loaded in BST-Gel for injection into the eye. BioSyntech is conducting clinical trials in Europe on two tissue repair products, BST-Fill, an injectable soft tissue filler for cosmetic and reconstructive surgery applications, and BST-InPod, an injectable shock absorber for restoring the cushioning property of atrophic plantar fat pads to relieve heal pain in the foot. BST-CarGel, an arthroscopically delivered product for repairing damaged cartilage, is in preclinical trials.

Chitogenics (Chatham, New Jersey) is clinically evaluating a biopolymer that is a derivative of chitosan for use as a preventive of post-surgical adhesions. The chitosan is derived from crustaceans that are harvested nearby its facility in Darmouth, Nova Scotia.

Bioland (Chungnam, Korea), a producer of plant herb extracts used in cosmetic applications, exhibited a range of tissue engineered and collagen-based products. They include: bio-artificial skin prepared from a collagen scaffold and a skin tissue culture, a bio-artificial cornea made from a collagen-amniotic membrane matrix, tissue models prepared from tissue culture human skin for use in safety testing, and biological wound dressings prepared from an amniotic membrane for use on partial thickness burns and as skin grafts.

Aastrom Biosciences (Ann Arbor, Michigan) promotes itself as "the cell therapy company." It develops cell-based products using patented technologies for stem cell tissue repair and for the treatment of cancer and infectious disease. Its technology platforms include a single-cell perfusion technique for generating cells having biological function and an automated system for delivering cells for therapeutic use. These technologies are integrated into the AastromReplicell system, which standardizes and automates processes needed to produce high quality tissue repair cells and therapeutic cells. It has CE mark approval and is available in the U.S. for clinical research programs and for companies developing cell therapies. Aastrom's pipeline of tissue repair cells, derived from bone marrow and cord blood, target the reconstruction of normal tissues and are intended for use in stem cell transplants for treating severe osteoporosis and for bone grafting procedures. Its therapeutic cells include the Dendricell dendritic cell products for the cancer vaccine market.

Nastech Pharmaceutical (recently relocated to Bothell, Washington, from Hauppauge, New York) is a developer of products for intranasal drug delivery. The company uses excipient-based methodologies and an approach described as "formulation science." It uses a novel intranasal platform for delivering large drug molecules that can currently only be administered by injection. The company is in a Phase I study for the intranasal delivery of interferon-a for multiple sclerosis, interferon- for hepatitis C and somatotropin, the human growth hormone. These are only three of 12 active investigational new drug programs announced by the company. Nastech reacquired from Schwarz Pharma (Monheim, Germany) rights to an intranasal scopolamine for motion sickness that has completed a Phase III trial. The company's intranasal vitamin B12, Nascobal, is being sold by Cardinal Health (Dublin, Ohio) for treating pernicious anemia. Nastech is in Phase II trials with intranasal apomorphine for treating male and female sexual dysfunction. The product is licensed to Pharmacia (Peapack, New Jersey) and the attendees were reassured that the product will continue to be developed even after the pending acquisition of Pharmacia by Pfizer (New York), which markets the highly successful drug, Viagra, for male erectile dysfunction. Nastech has a Mammary Aspirate Specimen Cytology Test that has FDA clearance for use in breast cancer detection. This hand-held device collects cells from a woman's milk ducts for cytological examination. Nastech is prepared to divest this non-strategic asset.

EpiCept (Englewood Cliffs, New Jersey) is developing topical prescription analgesics, delivered as creams or patches. The company is conducting Phase II clinical trials in the U.S., Canada and Europe for lidocaine patches to treat post-operative pain and acute back pain and for a cream containing amitriptyline and ketamine to treat neuropathic pain caused by inflammation or damage to peripheral nerves.

Encision (Boulder, Colorado) markets the AEM instruments that enable surgeons to perform electrosurgical procedures more safely when using conventional laparoscopic instruments. The instruments incorporate active electrode monitoring technology to prevent patient burns when performing minimally-invasive surgery. The market for electrosurgical instruments used in minimally-invasive surgery is estimated to be $400 million annually. Converting to AEM laparoscopic instruments does not require any change in surgical technique or operating room protocols.