The Need for Synthetic Tracheas

HART is a clinical stage regenerative medicine company developing organs for transplant.

The first product, the InBreathTM Airway Transplant System, is intended to be used to restore the structure and/or function of a severely damaged airway. The InBreath System is comprised of a porous plastic scaffold made in the size and shape of the natural trachea, bronchus or tracheobronchial tree and a rotating bioreactor used to seed the patient’s own bone marrow cells onto the scaffold prior to implant.

We believe the InBreath System is the first to enable the application of regenerative medicine techniques to the production and transplant of complex, three-dimensional human organs like the trachea. The InBreath bioreactor technology has been used in excess of ten successful human airway transplant surgeries and the most recent of these surgeries also used our InBreath scaffold.

We believe that the first of the surgeries conducted in 2008, was the world’s first transplant of a regenerated airway. This surgery used a human donor trachea as the scaffold. In addition, we believe the second surgery, conducted in 2011, was the world’s first transplant of a regenerated airway using a synthetic scaffold.

The patients who received these two airway transplants are alive at more than five years and more than two years, respectively, following their surgeries, and each of these surgeries was published in The Lancet, one of the world’s most respected peer-reviewed medical journals. The third, fourth, fifth and sixth surgeries also used our bioreactors and used a second generation synthetic scaffold that was made of fabric rather than the solid/porous construction used in the second surgery. As of September 9, 2013 three of these four patients are alive. The one who did not survive died of underlying causes unrelated to the bioreactor or scaffold. The seventh, eighth, ninth and tenth surgeries used our bioreactors and third generation scaffolds, which were the first scaffolds manufactured by HART to be used in any human surgeries. Three of these four patients are alive. The one who did not survive died of underlying causes unrelated to the bioreactor or scaffold.

The first six surgeries took place in Europe and Russia. The seventh surgery was the first in the US and took place in April 2013 at Children’s Hospital of Illinois in Peoria with FDA approval under an investigator-led Investigational New Drug application, or IND.  The three subsequent surgeries were performed in the third calendar quarter of 2013 in Europe and Russia. All surgeries to date using our technologies have been led by Professor Paolo Macchiarini, a world-renowned thoracic surgeon of the Karolinska Institutet, one of Europe’s leading research hospitals.

Our products are currently in development and have not yet received regulatory approval for sale anywhere in the world.

We believe our technology could enable surgeons to cure nearly all primary trachea cancers. Our products address the critical challenges to trachea transplant: the shortage of suitable donor tracheas and the risk and expense of lifelong anti-rejection drug therapy. Because the scaffolds are synthetic, our technology will eliminate the need to wait for suitable donor tracheas. Our technology also obviates the need for anti-rejection drug therapy because the surgeon uses the patient’s own bone marrow cells to seed the scaffold. In addition, patients with trachea cancer treated using our products have not required either chemotherapy or radiation therapy after the transplant, thus potentially eliminating the significant side effects and expense of such therapies.

Because these substantial costs and risks can be reduced or even eliminated with our technology, we believe our products can both help save lives and reduce overall healthcare costs. None of the surgeries using our products have involved human embryonic stem cells and we do not currently expect surgeons to use such cells with our products.

Trachea cancer is a devastating and almost always fatal disease. Current treatments such as radiation therapy, chemotherapy and surgery have poor outcomes, resulting in median survival of only 10 months and a five-year survival rate of only 15%. Trachea cancer is one of the most fatal of all cancers with 5-year survival rates far below those of breast cancer, prostate cancer or colon cancer. Surgically removing a tracheal tumor is often the best way to treat tracheal cancer. However, surgery generally cannot be performed if the tumor is more than 2cm (about ¾ of an inch) in diameter because the remaining tissue cannot be stretched enough to bridge the gap left by removing the tumor. Because it is hard to detect trachea cancer in its early stages, many patients are only diagnosed when the tumor is already too large to be surgically removed. In these cases the patients receive palliative treatment only and typically survive less than a year. These patients are the vast majority of trachea cancer patients and we believe that the InBreath Airway Transplant System could enable surgeons to cure nearly all primary trachea cancers.

According to an article published in The Annals of Surgical Oncology in 2009, the incidence of trachea cancer is approximately one per one million of population, reflecting an addressable market of approximately 900 trachea cancer patients per year in the developed world. In addition, the incidence of bronchial cancers is estimated in published articles to range from 0.1% to 2% of lung cancers. We believe we have been conservative in estimating the number of bronchial cancers at 0.2% of lung cancers reflecting an addressable market of approximately 1,500 bronchial cancer patients per year in the developed world. Therefore, we estimate the total addressable market for trachea and bronchus cancer combined is approximately 2,400 patients per year in the developed world. In addition to trachea cancer, certain types of trachea damage can be treated by transplanting a trachea. In particular, patients may receive a tracheotomy, or surgically created hole in their throat, to allow them to breathe. When the tracheotomies are in place for more than a few days, patients are at increased risk of dying from pneumonia caused by aspiration of foreign material into the lungs. We estimate that there are approximately 3,900 trachea damage patients per year worldwide. In addition, there are approximately 250 patients in the developed world who are born without a trachea, a condition called tracheal agenesis, who may be treatable with a trachea transplant.

Combining patients with trachea and bronchial cancer, trachea trauma and tracheal agenesis, we estimate the total addressable patient population for airway transplants using our products is approximately 6,500 per year. While we cannot predict what the total potential market will be when and if we obtain regulatory approval to market our trachea products, based solely on there being at least 6,500 patients per year at the time of such approval, we estimate the total potential market for airway transplants that use our products could exceed $600 million per year if we were able to charge at least $100,000 per procedure for the InBreath System. While these estimates capture the number of new patients annually that are candidates for transplants using our products, they exclude what we believe to be a much larger pool of existing potential patients.

Patients with trachea cancer typically are treated with radiation therapy, chemotherapy or a combination of both. There are a number of common significant side effects of radiation therapy and chemotherapy, including pain, fatigue, hair loss and kidney and bladder problems. Such therapies are also expensive, with chemotherapy alone typically costing $24,000 per patient annually. Even with these therapies median survival is only 10 months.

While surgery is a preferred treatment option for trachea cancer, it is rarely performed because most trachea cancers are not diagnosed until it is too late for surgery to be a viable option. A trachea or bronchus transplant has also not been a viable option to date due to the difficulties of finding an anatomical match between the donor and the patient. Even if a donor trachea were available, the patient would require anti-rejection drugs for the remainder of his or her life to prevent rejection of the donor trachea. This therapy is expensive, typically costing $20,000 to $30,000 per patient annually. There is also a risk to the patient as anti-rejection drugs suppress the immune system causing even a mild infection to become potentially life threatening.

Previous attempts to implant a tracheal prosthetic have been unsuccessful in improving long-term survival as they have been unable to allow the body to create a functional lining of the trachea which is essential to the clearance of mucus. Without the clearance of mucus, patients have poor prognosis and typically die from pneumonia or respiratory failure shortly after transplant.

Patients that contract aspiration pneumonia caused by tracheotomies are treated with antibiotics that often fail, leading to the death of the patient. Trachea transplant is almost never used to treat these patients today due to the lack of suitable donor tracheas.

Nearly all patients that are born without a trachea die within a few minutes of birth due to lack of oxygen. On rare occasions a hole forms between the patient’s esophagus and lungs that can allow a surgeon to insert a breathing tube to connect the lungs with the mouth. However, we know of no patient born with tracheal agenesis who has survived more than six years.

Our Solution

We believe the use of the medical device products we are currently developing, together with the patient’s own cells, will provide a system for surgeons that is a major advance over the current therapeutic options for treating trachea cancer and trachea trauma and may be applicable to other medical conditions requiring organ transplants. We believe our products are the first to enable the application of regenerative medicine techniques to the production and transplant of complex, three-dimensional organs like the trachea. With continued development, we believe that our technologies will be applicable to the repair or transplant of other important human organs such as the lungs, gastrointestinal tract, heart valves, and heart. Our bioreactor technology was used in both the world’s first transplant of a regenerated airway in 2008 and in the world’s first transplant of a synthetic regenerated airway in 2011. The complete InBreath System combining our scaffolds with our bioreactors was used for the first time in April 2013.

We believe our products will overcome the major challenges in trachea and other organ transplantation. Unlike traditional organ transplants, our products will eliminate the need for a donor because the scaffold will be manufactured in a factory. In addition, for hollow organs, such as the trachea, our technology enables the production of a transplant that precisely matches the patient’s anatomy. Because the surgeon uses the patient’s own bone marrow cells to seed the scaffold, our technology also eliminates the risk and expense of lifelong anti-rejection drug therapy. In addition, patients with trachea cancer treated using our products have not required either chemotherapy or radiation therapy after the transplant, thus eliminating the significant side effects and expense of such therapies. Because these substantial costs can be reduced or even eliminated with our technology, we believe our products can both help save lives and reduce overall healthcare costs.

Further, human embryonic stem cells have not been used in any of the procedures involving our trachea transplant products. This eliminates both the medical risks and ethical controversy associated with regenerative medicine approaches using human embryonic stem cells and other controversial sources of cells.

We believe the use of our products together with the patient’s own bone marrow cells solves both the major challenges facing organ transplant: a synthetic scaffold avoids the need to wait for a donor and the use of the patient’s own cells avoids the risk and costs of anti-rejection drug therapy. The first application of our products is in treating trachea cancer but we believe the technology can be developed to apply to other important human organ transplants as well.