![[Note - This is a left-handed helix, don't use - SdC] DNA Double Helix](https://legacy.xconomy.com/wp-content/images/2015/05/DNA-image-Used-with-permission-from-Depositphotos_Denrud-125x125.jpg)
Intellia Therapeutics, a developer of human medicines based on the gene editing technology CRISPR-Cas9, has thrown its hat in the IPO ring. It’s also shooting directly at the liver.
The Cambridge, MA-based company filed paperwork to go public today. It also announced a deal with Tarrytown, NY-based Regeneron Pharmaceuticals (NASDAQ: [[ticker:REGN]]) to develop a therapy for a rare liver disease, bringing $75 million immediately into Intellia’s coffers.
CRISPR-Cas9 became a mainstream fascination last year not just because of its potential to cure a number of genetic diseases, but also the possible ethical perils of genetic tinkering. Yet a handful of companies have moved forward with noncontroversial programs to go after diseases without messing with eggs, sperm, or human embryos—the so-called “human germline” that many feel is taboo, at least for now.
Intellia is one of those companies. Its Cambridge neighbor, Editas Medicine (NASDAQ: [[ticker:EDIT]]), forged ahead with an IPO in February, raising $94 million. Intellia has set an initial IPO goal of $120 million, although there’s no guarantee its debut—if it happens at all—will end up at that lofty amount.
A third CRISPR-Cas9 company, Crispr Therapeutics, with offices both in the U.K. and Massachusetts, could follow soon, having already raised nearly $100 million in private funds and sealed two big partnerships.
Intellia has decided to run full-bore at an area that many in the gene editing field have said will be a difficult target. It wants to send the gene-editing machinery of CRISPR into liver cells, via a patient’s bloodstream, and make cuts in DNA that help fix diseases that originate in that organ. The Regeneron deal could span several programs, but the first joint project aims to treat a disease called transthyretin amyloidosis (ATTR). ATTR is one of three specific liver diseases Intellia says it is targeting, and it also happens to be the target of a Phase 3 program from Alnylam Pharmaceuticals (NASDAQ: [[ticker:ALNY]]).
Intellia wants to deliver CRISPR into liver cells using technology called lipid nanoparticles, or LNPs, that it licensed from Novartis, its largest corporate partner.
The firm is also pursuing the liver diseases alpha-1 antitrypsin deficiency and hepatitis B infection, and it says it is exploring treatments for a group of diseases called inborn errors of metabolism, which are typically rare diseases caused by a single gene gone awry. In its IPO paperwork filed this afternoon, Intellia says it would like to have one or two liver-focused programs pointed toward clinical trials in the next 12 to 24 months.
The CRISPR race to the clinic is on. Editas has said it aims to have its first program, for a rare form of blindness called Leber congenital amaurosis, in clinical trials by 2017.
Firms also want to use CRISPR to edit cells outside the body for greater therapeutic powers then reintroduce them into patients. Intellia has a wide-ranging deal with Novartis to develop treatments that use modified T cells, known as CAR-T, and hematopoietic stem cells. Editas is working with Juno Therapeutics (NASDAQ: [[ticker:JUNO]]) of Seattle to create next-generation CAR-T cells, as well.
One goal before any of these programs can be tested in people is a reasonable assurance that the enzyme Cas9, which serves as CRISPR’s molecular scissors, is actually cutting DNA where it is meant to cut. There is great debate among researchers and drug developers how much off-target activity should be considered unsafe—potentially causing DNA damage instead of repair—and whether that activity is detectable.
When asked if he and his peers are using CRISPR-Cas9 to edit T cells for cancer experiments, Cameron Turtle, an oncologist and researcher at the Fred Hutchinson Cancer Research Center in Seattle, said not yet. “We need to see better specificity”—that is, more accuracy hitting the right spot—“and improvements in the engineering of CRISPR-Cas9 systems.” Turtle has worked on T cell programs affiliated with Juno.
The entire field is moving fast. CRISPR, long known as a bacterial defense system against invading viruses, emerged four years ago as a potential system for editing the DNA of all sorts of organisms with a paper from researchers Jennifer Doudna of the University of California, Berkeley, Emmuanuelle Charpentier, and others. Doudna has since founded Caribou Biosciences, of Berkeley, CA. Caribou holds exclusive rights to the Berkeley share of the IP, and it licensed therapeutic use to Intellia, which launched in late 2014 after incubation within Atlas Venture. Those IP ties mean that Intellia has a lot riding on the big CRISPR patent fight, which pits The Broad Institute against Berkeley, the University of Vienna, and Charpentier. If the U.S. Patent and Trademark Office rules in favor of the Broad, Intellia’s rights could be curtailed.
Caribou is the largest shareholder, with a 21.5 percent pre-IPO stake. Next in line is Novartis (20.3 percent), Atlas (17 percent), OrbiMed Advisors (9.3 percent), and Fidelity (7.1 percent). Nessan Bermingham, the former Atlas partner, leads all management with a 3 percent stake.
