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The revolutionary biotechnology that processes DNA inside a living human organism

By Aayushi Pratap

John Leonard, CEO of Intellia Therapeutics, has just emerged from a long meeting at the company’s headquarters in Cambridge, a leisurely five-minute jog from the MIT campus. He stretches his arms, crosses his palms and brings them behind his head. For now, the 64-year-old is relaxed. But he immediately comes back to life when he begins to explain how science can process DNA using markers, a rag, and anything else he can find that can help him make his point. “Sometimes I’ve also used my wife’s necklaces,” he says.

Leonard suggests imagining human DNA as a necklace of 3 billion beads and four different colors. “The challenge is how to find 20 beads to the exclusion of all others,” he adds. The beads he refers to are genes, which give cells the necessary instructions to function.

Many companies are using Crispr, a revolutionary method of precise DNA editing that formed the basis for the 2020 Nobel Prize in Chemistry, to knock out disease-causing genes in the laboratory and then inject the “repaired” cells back into the patients. Intellia does that too.

However, another Intellia gene-editing platform has attracted Wall Street’s interest. The $3.6 billion company has found a way to use Crispr outside the lab, inside a living human organism. Their method could have important implications for the development of new drugs for genetic diseases that are currently partially or completely treated by treatments.

“Intellia is the first company to do in vivo genome editing systematically. In my opinion, that’s the real differentiator,” says Jack Allen, an analyst at Baird Equity Research.

Despite the innovative gene editing technology, the company faces serious problems. Over the past 12 months it has lost $277m on revenue of $33m. Its revenue has been falling quarterly since 2020, while losses are widening. The company has raised a total of $1.8 billion, on top of the $115 million it raised in 2016 when it went public, and still has $1 billion in cash. At current rates, however, this fuel will last her for two years.

Intellia has a promising drug in early stage clinical trials, but about 90% of treatments at this stage do not reach the market. At the same time, the patent battle for its basic technology is taking place.

All of this sounds ominous enough, as a result of which Intellia’s stock has plunged 62% just before the end of the first half of the year, when the Nasdaq has lost 23% and the Nasdaq biotech index has lost 24%.

However, Intellia has an ace up its sleeve: the man who runs the company is aware of these challenges. Medically trained, Leonard has a track record few in the industry can match.

In 1992 Leonard joined Abbott: his team’s research won FDA approval for the anti-HIV drug Norvir/Kaletra, which helped curb the AIDS epidemic in the 1990s. In 2013, he joined Abbvie, the biopharmaceutical unit spun off from Abbott that played a key role in the development of Humira – a drug with sales of $21 billion in 2021, putting it in first place worldwide.

“I worked on Humira for 13 years,” says Leonard. “I learned a lot about an organization. What makes it work. What makes it sometimes not work.”

His experience in bringing blockbuster drugs from the lab to the market could propel NTLA-2001, which Intellia is jointly developing with Regeneron Pharmaceuticals, to success. It is an injectable gene-editing treatment for ATTR amyloidosis – a rare genetic liver disease that affects 1 in 100,000 Americans and kills about 850 of them each year.

In 2019 the market for the treatment of this disease amounted to $585 million. Today it is estimated that the number of people suffering from this disease has increased, but there are gaps in diagnosis. Better diagnostics would grow the market, increasing its value to $14.1 billion within 7 years, according to a report by London-based consultancy GlobalData.

So far there are three FDA-approved drugs that slow the progression of the disease, but none of them is a permanent cure, and patients often need a liver transplant. In February Intellia released the first data from its clinical trials, which showed a lasting, positive effect on participants, with no worrisome side effects.

Despite the promising data, the road for Intellia is not paved with roses. The company licenses Crispr technology to perform in vivo gene editing from the University of California, the University of Vienna, and researcher Emmanuel Charpentier (the “CVC” group, as it’s called). University of California biochemist Jennifer Doudna, who shared the Nobel Prize with Charpentier for the discovery of the Crispr processing system, is a co-founder of Intellia, although she has limited day-to-day responsibilities.

The CVC group’s patents have been the subject of legal challenges. The patents obtained by the CVC team conflict with those of the Broad Institute, the medical research center founded by the late billionaire Eli Broad and affiliated with Harvard and MIT. In 2016, a legal battle began, with tens of millions of dollars in royalties at stake, over who first invented Crispr used in human and plant cells. In more than 80 countries, including China, Japan and the 27 countries of the European Union, a decision has been issued attributing the patent to the CVC group. In the US, however, a recent decision by the Patent Trial and Appeal Board (PTAB) sided with the Broad Institute. The CVC team has appealed. “Fortunately, this decision does not affect the development of Crispr at all,” says Doudna. “Investors continue to put money into the sector,” he adds.

Of course, even if Intellia loses in court, it will still be able to get a license for the technology. “Anyone not licensed by the Broad Institute and conducting work with [το Crispr], he should probably get it at some point. I imagine that’s also true for Intellia,” explains Jacob Sherkow, a law professor at the University of Illinois.

Leonard sees the future beyond the intellectual property battle. He is focused on growing the company to include treatments for other diseases, such as hereditary angioedema, hemophilia, blood and ovarian cancer.

But first, Leonard will have to sort out the patent chaos and raise more money. The prospects opened up thanks to Intellia’s technologies make him optimistic. “I think when people are asked to decide where to put their cash to make it work, they look at how feasible the outcomes of the programs are [ανάπτυξης φαρμάκων] to reach the market. We’re definitely in that category of company,” Leonard says. “We believe the company is on track to continue to be funded as we move forward.”

Leonard is even more optimistic about the future of Crispr-based drugs, which have the potential to consign a number of deadly diseases to the “time closet” of medical history. “In the coming years, we will not be limited by technology, but by imagination,” he points out.

Source: Capital

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