Bypassing The Debate
I wanted to write a series of case studies on startup biotech companies that are focused on stem cell research. Revivicor intrigued me because of their novel approach to stem cell isolation. Their regenerative medicine approach has potential to bypass many of the heavily debated ethical issues surrounding the use of embryonic or fetal tissues, as is done in therapeutic cloning. Being situated in the USA, this is important, since the past few years have been ripe with debate on this topic. The debate has heated up particularly in recent years, starting with the passing of a bill (House of Representatives, in May 2005, Senate, July 2006) to loosen limitations on embryonic stem cell research, and the subsequent veto by President Bush. The House has continued attempts to pass similar bills into 2007.
Revivicor describes itself as an early-stage biotechnology company developing engineered tissues and whole organs for human transplantation. In fact, the company is privately-owned spin-off from PPL Therapeutics, famous for having produced “Dolly”, the world’s first cloned sheep. Formed in 2003, Revivicor included 25 professionals from PPL’s US division in Blacksburg, Virginia, in addition to a Pennsylvanian subsidiary. It consists of Revivicor Holdings, a Delaware company, under which Revivicor Inc. of Virginia is the primary operating subsidiary and the core research and development arm. Clinical work is performed by Revivicor Inc. of Pennsylvania at University of Pittsburg Medical Centre (UPMC).
World Leader in Animal Cloning and Transplant Technology
In addition to its stem cell projects, Revivicor leads the field in cloning transgenic pigs and production of whole organs and therapeutic cells from pigs. Much of their research is on prevention of hyperacute rejection (HAR) in cross-species transplantations. They aim to perform pig-to-primate transplant studies, islet cell transplants for reversal of diabetes, and possibly begin human clinical trials, within the next 2 years.
At the beginning of this decade, Revivicor was also involved in research on the use of skin cells and a process of “de-differentiation” to restore them to a pluripotent state, i.e. stem cells. It was intended that these IPSCs could then be used to generate differentiated tissues of different organs that would be produced for transplants and regenerative treatments.
The Stem Cell Program
Revivicor’s stem cell research is based on “cellular reprogramming”. They use skin cells as precursers, because of the ease of obtaining them from any subject. The technology proof of concept was demonstrated for the de-differentiation approach using rhesus, porcine and bovine cells. The stem cell program was supported through a grant from the US Department of Commerce Advanced Technology Program (ATP) and, according to the Revivicor website, consisted of $1.9 million over three years ending January 2004. The regenerative medicine approach, as opposed to therapeutic cloning using fetal/embryonic stem cells, appeared to have enormous potential because of its ability to bypass the ethical restrictions of cloning.
Revivicor gets its support from an investment group led by the UPMC, which owns 31% interest. The balance of the group consists of Highmark Health Ventrues Investment Fund, L.P., and Fujisawa Investments for Entrepreneurship, L.P.
According to CEO Dr. David Aayres, ATP has also been critical to the survival of Revivicor. The company has obtained four grants in total from ATP. The xenotransplantation research project, focused on production of organs and tissues from cloned, genetically modified pigs, for human transplantation was funded in part from a $2 million ATP grant received by PPL in November 1999. The grant for stem cell research was the second ATP grant obtained by Revivicor. A third grant of $1.9 million over 3 years, was awarded to fund further work on the development of safe therapeutic products from pigs for xenotransplantation. In September 2004, a 2 year grant of $1.8 million was obtained for research utilizing Revivicor’s platform technologies in gene knockout and somatic cell nuclear transfer to inactivate the antibody producing genes in pigs and replace them with the human equivalents. This work is also funded in part (3 years, $3.1 million) by the US Dept. of Defense (DARPA). The goal is to produce human polyclonal antibodies as potential vaccines against biowarfare agents (i.e. anthrax), and infectious viruses like HIV and hepatitis. Revivicor retained rights to commercialization of all non-military applications of its gene knock-out animals, which can be used against a broad range of infectious diseases. The market for this work was projected by Revivicor to be worth over $5 billion by 2010.