Biotech and Ebola in Cambridge: Chris Garabedian, CEO of Sarepta

By Aram Arkun

Mirror-Spectator Staff

CAMBRIDGE, Mass. – Recently, the Ebola virus has been in the news almost every day, with panicked speculation about the danger of its spread, and the ethics of treatment. There is no tested and proven treatment or vaccine available. Christopher “Chris” Nishan Garabedian, the president and chief executive officer (CEO) of Sarepta Therapeutics, is frequently sought out by the media in these discussions. It happens that his company is one of only a handful with drugs that could treat Ebola victims. Garabedian, in his Cambridge headquarters, explained that in fact this drug is only one example of what his company can accomplish. Sarepta employs an approach which is part of a revolution in biotechnology, using Ribonucleic Acid (RNA) to specifically target diseases and genetic problems.

This is a different technology from the ZMapp combination of several antibodies against the Ebola virus, which was in the news because it was given to two American missionaries infected by Ebola recently. These antibodies attempt to allow a person’s own immune system to identify and neutralize the virus. However, they had never been given to humans before, while Sarepta’s drugs have been used on non-human primates and in Phase 1 safety trials for the Federal Drug Administration (FDA), with promising results. The trials were supported by the Department of Defense but economic issues halted the program.

The problem is that treatments for many diseases which are usually restricted in the numbers of victims do not economically attract investments necessary to support research and trials. For this reason, drugs intended to treat rare diseases affecting fewer than 200,000 people in the US are called orphan drugs. Garabedian said, “I think the US government knows, as governments around the world know, that to leave it up to the private sector to develop technologies and medical countermeasures against these threats, whether pandemic threats that spread naturally or biological ones that someone can manufacture in a garage, is not feasible. They know they have to foot the bill. The problem is that they are not funding it fully.” He pointed out that crises come and go, so specific diseases float in and out of the public’s awareness along with a sense of urgency, but the potential threats remain.

For Ebola in particular, his company has enough supply ready only to treat 100-150 people, if the FDA would give emergency authorization, along with permission from the Department of Defense which had provided initial funding. In case Ebola does spread on a greater scale, he said, “We hope that this is raising awareness that we have the technology but need to raise the manufacturing ability to a higher scale.”

The same is true of course for Ebola drugs using different approaches which are being developed by a few other companies, like Tekmira’s TKM-Ebola, which the FDA very recently allowed to be used on infected people. However, Garabedian exclaimed that “regardless of what press or market reactions have been, we still think that we have the most advanced and robust data set for safety and efficacy that is out there for Ebola.”

There are many companies utilizing various types of technologies that attempt to modify or suppress RNA. Sarepta uses phosphorodiamidate morpholino oligomers (PMOs), stable synthetic chemical structures similar to RNA. They can be used to create drugs specific for either human or pathogen RNA and can also target specific tissues. PMOs increase or decrease the production of a protein involved in a disease. In the case of Ebola or other viruses, the PMOs block access of the virus to human cellular machinery and thus inhibit its replication.

Despite the attention that it is garnering lately, the work on Ebola or related viruses like Marburg is not the main focus of Sarepta’s commercial research. Instead, it is pursuing PMO-based therapeutics actively for a form of muscular dystrophy called Duchenne (DMD), which is caused by a mutation or error in the gene for dystrophin, a protein necessary to protect human cells during muscle function. The PMO treatment in this case deals with human and not virus RNA, and is targeted to skip defective mutated sections of the dystrophin gene to allow the body to make functional dystrophin protein. It can be targeted to specific mutations, and thus treat different varieties of the disease. Phase IIb clinical trials on safety and efficacy have already been done on one of these drugs, eteplirsen, meaning that it is advancing in the FDA process needed for government approval.

Garabedian stated that the reason for the focus on DMD is that “Duchenne is a commercially viable market, high on medical need.” Furthermore, the same technology can be used for a series of related drugs. Garabedian said, “It is the consummate personalized medicine.”

This is novel for regulators like the FDA. He continued: “I would say that this technology demands a new approach from the FDA…If you read that we have had ups and downs, it is because the FDA sometimes gets more conservative the more advanced and novel the technology is. I have been characterized as being aggressive or pushing too hard, but all we were doing is arguing on behalf of patients who need this technology.”

Sarepta needs at least one successful breakout drug to allow it to expand the scale of its finances and work. Afterwards, it can expand its PMO-based approach to many different diseases and genetic problems, and will be in an enviable position. For example, among its other ongoing projects, Sarepta is testing a flu drug using the PMO approach.

There are many companies working on RNA therapeutics with different approaches. While some others also work with PMOs, Garabedian said, “We have the lion’s share of the real estate of morpholino intellectual property. We also have the most know-how on scale-up manufacturing. While we don’t have a 100 percent lock on all morpholino, we are the only one in advanced drug development. We have patents.”

Born in 1966 and raised in the Washington DC area, Garabedian is Armenian on both his mother and father’s sides. His parents were born in the US but his grandparents fled the Armenian Genocide to the US via Ellis Island and Cuba. He did not get to know his grandparents well, as they died either before he was born or while he was still young. Garabedian’s parents tried to instill Armenian culture in their children, but by the time they came to Chris, it became too difficult. For this reason, Garabedian said, “Peter Balakian’s Black Dog of Fate resonated with me. I too grew up with American cultural mores, and came to appreciate my Armenian heritage as an adult.” He started to read books, and saw movies like Atom Egoyan’s Ararat, and encountered in the popular culture efforts at documenting the Armenian plight. He did work for around a year from 1998 to 1999 for an Armenian, Vaughn Kailian, CEO and president at COR Therapeutics, but otherwise has had little opportunity to cultivate his Armenian connections in his profession.

Garabedian had a business background in college and initially worked in market research, brand management and new product development. He described his involvement in biopharmaceuticals as “a little bit of serendipity.” He began learning about this industry in a consulting company, and from 1994 worked at Abbott Laboratories in Chicago, which “was a great training ground….Then Gilead Sciences called in 1997 and I joined them. This was my formative experience in the biotech industry. They really shaped a vision. At the time, they were less valued than Sarepta is today. They had a few more employees…They have about a 140 billion dollar market capitalization today. They built it on a relatively small footprint. … I really learned what it takes to build a successful biotech, how to build in a lean, smart way, and good, smart drug development. I learned from my mentors, like John Martin as CEO of Gilead.”

Garabedian found out through experience that many companies failed not due to problems with their technology, but how they applied that technology, the information they attached to a particular drug, and how they dealt with the regulatory process.

Garabedian joined Celgene Corporation in 2007, feeling they were on the same trajectory of success as Gilead, and became Vice President of Corporate Strategy. He led its first commercial acquisition of a company called Pharmion. He joined the board of directors of AVI (the predecessor of Sarepta) in June 2010 and became its president and CEO in January 2011.

So far, things have worked out pretty well at Sarepta. With a cutting-edge technology moving toward FDA approval, it had the top performing stock of all 2012. It rarely used to break over a market value of 400 million dollars, and now it has been operating at a valuation between eight hundred million to 1.8 one billion. Garabedian does not want a buyout, and tells investors that the company is woefully undervalued, so they should stick with it for the next five or ten years.

Garabedian nurtures grand ambitions for Sarepta, and for himself. He learnt from two highly successful chief executive officers, and so instead of staying as part of a good management team, wanted the opportunity to build the next great company, the equivalent of a Google or Apple: “What I’m driven by and what motivates me is to apply my experience in this industry, to take a technology that can be the next revolution in medicine. If I can see this developed to treat even one serious disease like Duchenne, I will feel pretty good. I think this technology can be applied to many diseases. We all strive to be part of being something bigger than ourselves. This industry, this technology and this company give me the opportunity to do that. I hope my children will be proud of it, that they may have sacrificed time with their dad for something bigger.”