Highlights

Focus on Tengion

Growing Organs from a Patient's Own Cells: Science Fiction?

tengion case study

Tengion, Inc., a company formed from groundbreaking basic and clinical research at Childrens' Hospital Boston, is turning the regenerative medicine dream into a reality.

Dr. Anthony Atala's pioneering work

When Dr. Anthony Atala, MD, applied to a one-year clinical fellowship program at Children’s Hospital Boston in the late 1980s, he was a reluctant researcher. His goal was to perfect his skills and pursue a career as a pediatric urologic surgeon. After several discussions with world-renowned pediatric urologist and Program Director Dr. Alan Retik, Dr. Atala agreed to join a two-year program that included a year of research. Little did he know that he would spend 15 years at Children’s, conducting groundbreaking research that has since revolutionized the field of regenerative medicine and that his work would become the basis for a company able to regenerate diseased and failing organs and tissues.

When Dr. Atala joined Children’s, the standard procedure for treating patients with neurogenic bladder (due to spina bifida, spinal cord injuries, multiple sclerosis, Parkinson’s and other diseases) as well as bladder cancer was to surgically augment or remove the bladder and replace it with a section of the patient’s bowel. This highly dangerous and complex surgery practiced since the 1800’s has serious and well-documented limitations, mainly due to the intestine’s physiological function to absorb urine and excrete mucus. Performing the bowel-for-bladder augmentation on children bothered Dr. Atala. It did not make sense to him to perform a surgery that was bound to create problems in a child with a 70 or 80 years life expectancy. Thus began Dr. Atala’s quest for a way to grow new bladders for his patients.

His journey was a long one and riddled with challenges. Dr. Atala decided to explore tissue engineering, which could use the patients’ own cells (autologous) and therefore avoid many of the problems associated with organ transplant, including organ rejection. His idea was to grow the autologous cells on a scaffold in the shape of the desired organ. Dr. Atala developed this innovative idea by optimizing the growth of the right type of cells in vitro, by determining the appropriate composition of the biocompatible scaffold, and by perfecting the prompt re-implantation of the cells on the biodegradable scaffold into the patient.

In 1999, Dr. Atala reported that these autologous bladders functioned well in large mammals for a full year--and that same year he inserted the bladder scaffold seeded with cells into the first of nine children with spina bifida. This clinical trial was the first ever to study a regenerated human organ. The successful implantation and multi-year follow-up data were reported in the prestigious medical journal The Lancet in 2006. The publication prompted worldwide media coverage about scientist’s ability to grow organs from a patient’s own cells. In addition, the Atala group had expanded their work to growing other autologous organs and tissues such as urethras, skeletal muscle, blood vessels and cartilage.

A start-up company: the best way to develop Dr. Atala’s technology

During this time, TIDO at Children’s protected the technology by actively filing patents and building a large worldwide intellectual property portfolio to cover all aspects of this complex work. The best route to successfully commercialize the technology was a subject of debate at TIDO. While former Director, Don Lombardi, favored the strategy of a start-up company that gives the broad technology the attention it needed, the former Director, Dr. Brenda Manning, was rooting for a deal with a large pharmaceutical company that has the necessary infrastructure and financial resources. They finally agreed to seek a venture capital firm with solid backing from leading investors, including a pharmaceutical company, partly to ensure that Dr. Atala would closely participate in the evolution of his technology.

A few months later they began discussions about an exclusive license agreement with Scheer & Company, a life sciences advisory firm, which had a track record of building a series of successful companies, and a network of institutional and corporate venture capital groups, including a long-standing relationship with Johnson & Johnson. Johnson & Johnson was and continues to be a tremendous supporter of Tengion and their involvement along with that of its other investors, has significantly contributed to the success of this technology. David Scheer, President of Scheer & Company, has served as the company’s Chairman of the Board of Directors since inception.

After one year of ongoing talks with TIDO, the worldwide exclusive license agreement to form a start-up called Tengion was signed in 2003. At the time of the deal, forty-eight patent applications had been filed by TIDO and close to $500,000 spent on the intellectual property portfolio. Scheer & Company recruited an experienced management team, with Dr. Atala as a member of the Board of Directors and the Chairman of its Scientific Advisory Board, and established headquarters in Philadelphia.

Tengion’s challenges and solutions

Soon after the agreement was signed, Dr. Atala moved to Wake Forest University in Winston-Salem, North Carolina, to direct the Wake Forest Institute for Regenerative Medicine. This led to the first challenge faced by Tengion—how to coordinate scientific research performed in Atala’s group at Wake Forest with the work of the start-up company in Philadelphia. This combined with the second and most significant challenge of establishing manufacturing capabilities for the production of autologous human organs was tricky. The possibility of outsourcing the manufacturing was contemplated but no organization had the necessary expertise.

Tengion was able to address both challenges by building the world’s first facilities to grow human organs: a small GMP facility in North Carolina that optimizes Dr. Atala’s work from Children’s and from Wake Forest, which currently produces the organs used in the clinical trials; and a second manufacturing plant in Pennsylvania for large scale production required for later-stage clinical trials and commercial operations. The construction and operations of these two new and unprecedented manufacturing sites are costly but allows Tengion to control its own destiny and to establish itself as the worldwide leader in its field.

Advancing the technology of growing organs from a patient’s own cells has not been an easy task. Several characteristics of Tengion’s product candidates make the development especially challenging compared to the development of traditional therapeutics such as small molecules or antibodies. The product, although ultimately a living and functioning organ in a patient, is an original combination of living material (the patient’s own cells) and non-living material (the biodegradable scaffold on which the cells are grown in the shape of the desired organ). The composition of both materials has now been worked out.

Tengion’s pipeline is oriented towards personalized medicine where patients are treated with autologous cells instead of the usual “one size fits all” therapeutics. The use of autologous cells and the strength of the scientific platform result in high diversity, both in the number of different products that are made and in the possible applications. The management team has had to make difficult strategic decisions to prioritize their expanding pipeline of organs and tissues, choosing to initially focus on the generation of the bladder as their first product.

Another difficult task for Tengion was the issue of reproducibility and quality control in creating the autologous organs. The process of generating these organs was effectively transferred from Dr. Atala’s work at Children’s to the company in a rapid and methodical manner to allow the company to initiate the production at their own manufacturing infrastructure. Tengion took Dr. Atala’s academic experience and created the standard operating procedures that regulated, complex manufacturing operations require to operate efficiently and safely. Tengion continues to hone its processes along with the involvement of Dr. Atala’s team and ongoing dialogue with the U.S. Food and Drug Administration and European medical regulators to elaborate clear guidance for this innovative technology.

Tengion: achievements to date

Even with these scientific, manufacturing and regulatory challenges, the company has made remarkable progress since its foundation in 2003. It is now a high-profile clinical stage biotechnology company focused on the development of neo-organs and of neo-tissues.

Today, approximately 100 employees are working at their headquarters and research laboratories both of which house their neo-organ production facilities. Tengion’s management team has raised approximately $150M from top biotech equity investors in four rounds of financing in August 2004, June 2006, September 2007, and October 2008 to support the company’s pioneering work.

Tengion was named a model of venture capital-backed innovation and success at the 35th Anniversary Celebration of the National Venture Capital Association, and, Co-founder, President and CEO, Steven Nichtberger, M.D., received the 2008 Ernst & Young national Entrepreneur Of The Year® award in the Emerging Company category.

Currently, the company's lead product candidate, the Tengion Neo-Bladder Augment™, based on Dr. Atala’s basic and clinical research at Children’s, is in Phase II clinical trials in pediatric patients with spina bifida, and adult patients with spinal cord injury. The European Medicines Agency has designated the Neo-Bladder Augment as an orphan medical product for the treatment of spina bifida and for the treatment of neurogenic bladder associated with spinal cord injury. In the next year, Tengion expects to begin Phase II clinical trials with its Neo-Urinary Conduit – a product designed to treat patients whose bladders are removed due to bladder cancer and who today have their replacement bladders rebuilt using bowel or intestinal tissue.

In addition to the Neo-Bladder Augment, Tengion is researching and developing additional cutting-edge product candidates. Preclinical data presented in May 2008 at the Annual Meeting of the American Urological Association demonstrated the ability to regenerate an entire bladder with Tengion’s Neo-Bladder Replacement™, a bladder replacement for patients whose bladders are being removed surgically due to disease, such as bladder cancer. Tengion is planning to initiate human clinical trials in the next two years for this technology. In addition, the company is working on Neo-Vessel™ and Neo-Kidney™ research projects.

TIDO thanks Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine; Dr. Alan Retik, Urologist-in-Chief at Children’s Hospital Boston; Dr. Brenda Manning, former Director of TIDO; Dr. Tim Bertram and Mr. Gary Sender, Senior Vice President, Science and Technology and Chief Financial Officer of Tengion, respectively; and Mr. David Scheer, Chairman of Tengion, and President of Scheer & Company, for their input on this story.

Link to Tengion website: www.tengion.com
Link to Scheer & Company website: www.scheerandco.com

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