On the wall in James Sapirstein’s office at Tobira Therapeutics hangs a map of the world held in place by dozens of pins. These pins, which trace the spread of AIDS across North and South America, Europe, Africa, and Asia, sketch a macabre travelogue of Sapirstein’s professional life. Starting long before he became the CEO of Tobira, Sapirstein has been to every location they mark, hunting and trying to eradicate one of the greatest scourges of our age.

Sapirstein has been battling AIDS for a quarter century, simultaneously repulsed and fascinated by the virus and its ability to find new ways to disable the one sentry we have against infectious diseases. And he is fascinated by the knowledge AIDS has brought us about infectious diseases in general. Because of AIDS and its trigger, human immunodeficiency virus (HIV), virology better understands how viruses attack and how they react to counter-attack.

But our knowledge has come at a terrible price. When he worked in marketing and sales at Bristol-Myers Squibb, pushing to get AIDS drugs into the routine of life in African hospitals and clinics, Sapirstein saw and heard things that would make even some hardened doctors queasy — like the stories of small children raped by men who believed that having sex with a virgin would cure AIDS in themselves. Such superstitions allowed AIDS a conduit to the entire continent, and then to other parts of the world where western science still has made little headway.

Tobira, founded in 2006 and headquartered at 214 Carnegie Center, is a pharmaceutical research and development company (meaning that it generates no income, relying instead on venture capital) building a line of drugs designed to stymie HIV. Rather than simply crush the virus Tobira’s drugs want to deny HIV entry into the immune system.

Unlike any other virus, HIV conquers the immune system itself. Access begins with a receptor called CCR5, which sits on the surface of CD4 cells (a.k.a., T-lymphocytes or T-cells) and functions as a “trafficker” for lymphocytes, a type of white blood cell. According to the American Medical Association, CCR5, in part, helps lymphocytes know where they need to be when a pathogen or antigen comes along.

But when HIV knocks, CCR5 opens the door. From here, the disease rewires immune cells. As the virus spreads, it decimates T-cells and, thus, the ability to fight off infectious diseases. In an uninfected body there are normally about 1,000 T-cells per deciliter of blood. When the system gets down to 200 per deciliter, it’s HIV, says Sandra Palleja, Tobira’s chief medical officer.

Palleja, a longtime HIV researcher who spent more than 15 years directly treating AIDS patients, says that it can take most of a decade between the time the virus enters the body until full-blown AIDS develops. By then, the patient has become more susceptible to rare and difficult-to-treat infections, as well as certain cancers.

Palleja, who earned her MD from Boston University, is the former head of the antiviral program for Japanese pharmaceutical company Shionogi.

She also has been a researcher at Triangle Pharmaceuticals and Roche Labs, and was the director of the infectious disease clinic at St. Vincent’s Hospital in New York.

The New York native also is a founding member of the Latino Commission on AIDS and has served on the New York City HIV Planning Council, the AIDS Drug Assistance program (ADAP) steering committee in New York State, and the national review panel for the Title III-B Ryan White CARE program.

The first attempts to fight HIV were complicated, multi-pill and multi-dose cocktails that prevented the virus from replicating and infecting new cells. “Like birth control for the virus,” Palleja says. The medicines were effective but not very potent. “Patients survived with therapy and died without it. This was the criteria for early drugs to be FDA-approved — survival benefit, but this benefit was not very long.” Indeed, life expectancies, even with treatment, were only a few years post-diagnosis, at most.

As research crept along, AIDS scientists were baffled by the fact that some, albeit a decided few, were immune to AIDS, despite having all the risk factors. The virus was in their bodies, but HIV was unable to unlock the immune cells. No one knew why until doctors noticed that those resistant to HIV infection, despite being exposed, had a genetic mutation that protected them.

The mutation is called CCR5-Delta32, a total absence of CCR5 that essentially forces HIV to rattle around in your body, perpetually looking for a place to alight. The discovery was huge. It meant virtual immunity to HIV, and it has guided most subsequent research into the disease. “This became of scientific interest as we tried to create the same environment in others to block HIV entry,” Palleja says.

There are, of course, some caveats.

Only about 1 percent of the world’s population has the Delta32 mutation, and in order for it to occur you A) must inherit it from both parents, and B) must be Caucasian. Delta32 simply does not occur in persons of color.

Another thing to keep in mind is that you can’t just remove CCR5 from your body.

But what if you could encase it? Sapirstein relates the process of infection with a house metaphor. Imagine your immune system as a house made entirely of locked doors. HIV has the keys to all doors whose locks could be opened by CCR5. You can’t just remove a door and put in a piece of wall, but consider what would happen if you put glue in the locks.

Tobira’s glue is a line of drugs that have become all the rage in HIV research labs. Interchangeably called CCR5 inhibitors or CCR5 antagonists, the drugs are part of a new class of medicines called anti-retrovirals that blanket CCR5, making it largely impenetrable to HIV. Tobira is but one company developing CCR5 inhibitors — Schering/Merck and GlaxoSmithKline/Pfizer have made great headway. Pfizer, in fact, got approval in 2007 to market the first CCR5 inhibitor in the United States, Selzentry.

But the battle against HIV is not consigned to only the CCR5 receptor. The virus has another target receptor called CXCR4, though it is only seen in patients with advanced HIV disease, Palleja says. CXCR4, in concert with CCR5, allows HIV an entry into the immune system. Through CD4, HIV can alter the glycoprotein gp120, which in turn allows the virus to bind to either CCR5 or CXCR4, depending on which receptor it’s after. The result, however, is uniform — access to the white blood cells.

Tobira is working on a more efficient class of antagonists that will be a once-a-day oral pill — the Phase II experimental drug TBR-652. The drug works on both HIV-related receptors, and also on CCR2, a receptor that is responsible for inflammation in chronic conditions, though not necessarily limited to HIV, Palleja says. Tobira plans to study TBR-652’s effects on the CCR2 receptor “to see if it can offer additional benefit, such as minimizing risk for metabolic syndrome, insulin resistance, and perhaps cardiovascular disease, as these conditions are becoming more common in people with HIV.”

TBR-652 is fresh off a good showing in San Francisco, where results of the drug’s trials were presented last week at a conference. The drug showed signs of reducing detectable levels of HIV in the blood, and of being generally safe and well tolerated, according to a report of the drug’s results by Calvin Cohen, research director at Community Research Initiative of New England/Harvard Medical School on February 19.

The study concluded that TBR-652 is promising enough to warrant further research. Whether these results will garner Tobira the money it needs to continue is yet to be seen, and it is nothing Sapirstein can discuss.

Still, even if all goes well, and even with his staff of eight (including two MDs), Sapirstein does not expect to see a truly marketable drug from Tobira for about four or five years. And even then, he says, it will be only the next step in an arms race Sapirstein is not sure we’ll ever win.

“AIDS will win until we find the vaccine,” he says.

The trouble with AIDS and the reason Sapirstein is so fascinated by it is its ability to adapt. HIV has an annoying habit of finding other doors, other keyholes, and other mail slots and slipping through to the open house of our immune systems. And the disease has exploited its own mutations — reactions to being attacked by drugs, mostly — to become a different AIDS than it was 30 years ago.

In all its forms, the disease has decimated parts of Africa, Eastern Europe, and Asia, where education about AIDS is almost non-existent or unheeded. AIDS researchers have been frustrated by the unwillingness of some cultures to accept western science’s explanations of how AIDS works, how it spreads, and how it could be stopped.

In the beginning of the epidemic, in 1982, before science could cool panicked heads, Americans came to odd conclusions about how people contracted AIDS. The one weakness AIDS has is that it requires direct contact, but before we knew that, even we, the most medically advanced society in the world, believed the disease could come from mosquito bites, sharing drinks, or even sitting on unclean seats.

Scientific rationality stepped in early here, but in less-educated, poorer parts of the world, science is still seeking an escape from the Dark Ages. What we in the west consider witch doctory and superstition is considered sacred knowledge in some parts of the world — ideas that simple prayers, or potions, or, as Sapirstein learned in Africa, ingrained beliefs that sex with a virgin will purify the blood, are proffered as a cure.

In Africa a woman who becomes infected with AIDS — regardless of whether she contracts it willingly or by force — is ostracized. The disease’s spread often is considered a woman’s fault, and men trying anything to cure it simply made it more widespread throughout the continent in the 1990s.

In this hemisphere treatment has advanced because of the fervor with which HIV was attacked by the first population to get it. Gays in the 1980s fought back with such zeal that scientists here and in Western Europe were forced to answer their call for a weapon, Sapirstein says. One of AIDS research’s most important and famous volunteers, in fact, is Steve Crohn, a gay California man whose resistance to the disease amid a lifestyle that killed every one of his friends earned him the nickname “The Man Who Couldn’t Catch AIDS.” Studies on Crohn and others like him led to the Delta32 breakthrough.

Still, there is much education ahead, and it would be a mistake to think that everyone knows or understands AIDS just because we live in the United States. As with anything, education about AIDS is best delivered to school children. However, as with anything, all education is not created equal.

Remember, AIDS thrives where education is lacking even in classrooms in inner cities right here in New Jersey. Sapirstein worries that not all kids are getting useful information, or are simply not listening. In districts such as Princeton or West Windsor-Plainsboro, he says, students are taught about health from an early age. In these districts, where education and grades are important to the parents and the students themselves, kids listen.

But what about Trenton? Or Camden? Or Newark? Such districts are riddled with truancy, and for every kid who heeds the warnings, there is at least one who probably never hears it in the first place.

Nationwide, AIDS rates in poor inner cities are incredibly high. In New Orleans, 3.2 percent of the population has HIV or AIDS. Rates in Washington D.C. are similar — and yet, Sapirstein says, AIDS is quietly eating away at inner cities because their populations are not as vocal as gays have been.

The ironic thing is that this indifference coexists with great leaps forward in knowledge, like the Delta32 discovery. It is ironic, Sapirstein says, because the combination of indifference in and about inner cities and news of advanced medicines has made American society complacent. We hear little about how bad AIDS still is here, and much about how far we’ve come to treat it. So no one is paying attention, especially when it comes to AIDS abroad.

But raw numbers belie the reach AIDS still has. Three percent of a city the size of Washington, D.C., is still more than 17,700 people.

Sapirstein is galled by the complacency, as well as society’s skewed priorities when it comes to infectious disease. The press has been awash in stories about H1N1 flu for most of the past year. That virus, according to the Centers for Disease Control, infected 200,000 people and killed 4,000 in the United States last year. By contrast, 470,000 people in the United States have AIDS (not just HIV) and more than 14,000 die from it every year. If swine flu had the reach of AIDS, Sapirstein says, no one would feel safe leaving his own house. And yet no one in the news is paying attention to HIV.

These are not the only unkind word Sapirstein has for the press, which he says has made drugmakers out to be a major bad guy in the healthcare debate. Then again, the drug industry has rolled over and taken it. “The industry has been too lax in fighting back,” he says. “Drugs make up only 9 percent of our healthcare dollars. People say it’s expensive, but how many people do we keep out of the hospital?”

But drugs really are expensive, you might say. “Of course they’re expensive, but it’s expensive to run a biotech,” Sapirstein says. “I have two MDs working here. It costs money to attract top minds, and I don’t apologize for bringing great products to the market.”

More than the press, Sapirstein takes issue with the way the State of New Jersey has let a once-flourishing biotech haven out to dry. Sapirstein came to New Jersey by way of New York at the end of the ‘70s, as did the virus he would end up chasing around the planet. Twenty years later he moved to California, leaving behind what he says was a thriving biotech industry.

That bustle was the reason he returned six years later. But New Jersey had changed. The Princeton area was, and still is, the capital of the biotech industry, but he’s not sure how much longer that will be true. This is, he says, a hard state in which to run a high-tech business. Overregulated and over-governed, New Jersey makes businesses like Tobira jump through a lot of hoops before they can move forward with projects.

On top of this, New Jersey punishes businesses with a well-meaning, but hopeless taxation system that pays for schools through property taxes. As those taxes make the state less affordable to residents, businesses become less able to draw good candidates, and less able to afford to stay here themselves. “There are too many towns and too many laws,” he says. “And it will get worse before it gets better.”

If Sapirstein’s assessment of the state’s antipathy toward businesses sounds like something a biotech lobby group would say, you’re right. Sapirstein sits on the board of directors for BioNJ, a lobby group for the industry, based in Trenton. BioNJ’s official position is one of collaboration with the state, but it has had to fight for certain things. The group is responsible for the state’s Tax Credit Transfer program, which allows companies that record big profits — such as a utility — to put losses on their books and transfer a portion of their income to biotechs like Tobira so that it can continue financing its research. The system is referred to as “net operating losses,” or NOLs.

Tobira is in the process of raising funds that Sapirstein hopes will carry the company’s research through 2012. The company began with $31 million in venture capital that it collected from four entities that have seen it through since 2007. It is seeking another $30 million now.

Sapirstein is happy that Governor Christie plans to keep NOLs alive, as well as the Business Employment Incentive Program, or BEIP, which provides 10 years worth of grant money to businesses that bring or develop at least 25 jobs. And while Christie seems friendly to business development so far, Sapirstein is cautious. Politicians have promised the moon many times, and the world is still waiting for it. All he knows for sure is that if New Jersey blows it, there are states eager to knock us off our perch as the world’s biotech capital.

California, for example, is “setting out a big welcome mat” for businesses, Sapirstein says. Incentives there are stemming an exodus of high-tech jobs that has sucked nearly 400,000 positions from the state in the past decade. And it is winning out over New Jersey when companies decide to consolidate. In the past few months alone, California-headquartered On Assignment, a staffing business for the healthcare and science industries, left Carnegie Center; NexMed, a maker of topical and transdermal drugs, left East Windsor for San Diego; and two Cranbury-based manufacturing outlets were closed when their California headquarters consolidated.

Sapirstein is hopeful enough about the future to stick with New Jersey, though he admits he has reconsidered once or twice. He even teaches a course in entrepreneurship at Biotechnology High School in Freehold, a 300-student vocational school designed to prepare students for college programs in the biotech sciences. He just wonders how many others feel as optimistic.

Born in Argentina, Sapirstein emigrated to New York as a child, when his father moved the family and started his career in the restaurant business. Sapirstein himself is the first in his family to attend college. He moved to New Jersey in 1979 and earned a bachelor’s in pharmacy from Rutgers in 1984. In 1996 he earned an MBA from Fairleigh Dickinson.

Sapirstein met his first AIDS patient, a black Haitian man who had lost so much pigmentation in his skin that he looked white, right as the disease became a public word in 1982. An undergraduate at the time, he met the man at Robert Wood Johnson Hospital and uttered, “This is the Black Plague.”

This observation has become a common comparison in AIDS research circles. Resistance to both AIDS and bubonic plague involves a genetic mutation that keeps the diseases from entering their target cells, and scientists studying how people survived such scourges as bubonic plague or small pox (which together killed about 35 percent of Europe’s population in the 14th century) were quick to connect similarities.

Sapirstein began his career at Eli Lilly before moving to Roche Laboratories (now Hoffmann-LaRoche) in Nutley. In 1996 he became the director of international marketing for infectious disease medicines at BMS. This was where he met his wife, Lauren, who sold HIV medicines for the company. She now stays home with their children in Manalapan.

It is also where Sapirstein got to know Africa. He helped develop BMS’ “Secure the Future” initiative, a $100 million philanthropic campaign in southern Africa for HIV. In the four years he worked at BMS, Sapirstein traveled to Africa frequently enough to almost make it his day job. When he first arrived in the latter half of the 1990s the epidemic was so intense that some scientists openly wondered if the continent could even be saved.

Sapirstein makes no effort to hide his pride over his role in helping to reverse HIV trends in places like Botswana. As part of BMS’ efforts to quell the spread of the disease, the company handed out untold numbers of drugs and invested in an education campaign targeted from the top down. A curious thing about Africa, Sapirstein learned, is that despite the presence of governments there, people still view themselves in an essentially tribal way, identifying with certain subsects of society more than the national governments.

To get the message through, Sapirstein worked with men considered tribal leaders. Efforts paid off, and HIV trends are in reverse in some parts of southern Africa. Sapirstein’s work with women as well earned him enduring thanks, and a gift that hangs on his wall near the map full of pins — a beaded tapestry given by a group of 100 African women in thanks for his efforts to help them.

Sapirstein left New Jersey to work for Gilead Sciences in Foster City, California, where he served as senior director of global marketing and continued to help launch HIV drugs. Two years later he moved to Massachusetts-based Serono, where he turned around a flagging biotech focused on HIV wasting (the process of losing weight because of HIV). He then spent two years helping to start a pair of biotechs in New York City.

By the time he returned to Princeton he had been to every continent but Antarctica. Over his career, though, HIV has changed. And as it has been all along, Africa has gotten the worst of it.

Viruses are notorious for their adaptability. They mutate when met with pharmaceuticals designed to wipe them out, or merge with similar viruses to form strains that beget future generations called clades, differentiated by letters. Clade A is the first, and as the letters advance, the virus gets more resistant to existing drugs.

In Africa, HIV is up to F, and is becoming something scientists fear — multi-drug-resistant. It happens when people infected by a virus, get treatment that does not eliminate it, and transmit it to someone else. Like two people with the Delta32 mutation passing it on, the heir is already resistant. People now are contracting HIV in an advanced clade that has survived attempts to eradicate it. And the more drugs that take a shot and fail, the more the disease mutates.

This is why Sapirstein says the virus will likely not be erased. It learns too quickly, grows too aggressively. He is worried that the future will bring multi-clade versions of HIV and that the poorest and least educated will continue to inherit a disease that is several paces in the lead.

Sapirstein is not a pessimist, though. He is on the advisory board of Prescription For Hope, a non-profit supplier for African HIV/AIDS patients, and a tireless advocate of suppression education. He has been part of 23 major drug launches, six of which are related to HIV, and he is unapologetic about the effects of his career. Through BMS, he says, he was part of an effort that has saved more than 100,000 lives.

And yet, he is unsatisfied with where we are. AIDS medicines these days can add 25 years to a person’s life, as opposed to the two or three offered by early treatments. But Sapirstein asks this: “Is that all we’re supposed to give people, 25 years?”

Tobira Therapeutics, 214 Carnegie Center, Suite 306, Princeton 08540; 609-897-1102. James Sapirstein, CEO. www.tobiratherapeutics.com.

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