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Intellia’s early CRISPR trial data validates the drug pipeline and gene editing fields

An Intellia Therapeutics gene editing therapy that is injected into the patient and circulates throughout the body is now available Early data A small clinical trial has shown that it can safely and effectively perform editing in patients, which has brought verification for the company and its technology as well as the broad field of gene editing.

The experimental therapy NTLA-2001 is under development to treat transthyretin amyloidosis or ATTR, which is a rare genetic disease that can cause transthyretin to misfold. This misfolded protein accumulates in the body, especially nerve tissue and the heart, and becomes fatal. Intellia’s therapy aims to use CRISPR to inactivate the genes that cause ATTR, which may provide a cure.

The first phase of the study is being conducted in the United Kingdom and New Zealand, and preliminary results are to use two doses in 6 patients, each for 3 patients. In the low-dose group, blood levels of TTR decreased by an average of 52% on day 28. In the high-dose group, the average reduction was 87%, and one patient had a reduction of 96%. The study also proved safety, with no evidence of adverse events or liver toxicity.

Intellia, based in Cambridge, Massachusetts, presented the preliminary results of the first phase at the Annual Meeting of the Society of Peripheral Neurology on Saturday.They at the same time Publish In the New England Journal of Medicine.

“This is the first time that CRISPR-based in vivo gene editing has been demonstrated in the human body,” said Julian Gilmore, a professor of medicine at University College London and the national coordinating investigator for the first phase of the study, on Monday’s Intellia conference call. These findings provide a proof of concept for a promising new treatment strategy.”

ATTR is hereditary and caused by mutations in the TTR gene. Gilmore said the disease affects approximately 50,000 people worldwide. In some cases, ATTR is acquired, although the prevalence of this “wild type” is unclear. Wild-type ATTR mainly causes cardiomyopathy. Intellia’s research on genetic ATTR is continuing, and higher doses will be tested, with the goal of achieving greater TTR reduction. Gilmore said that higher doses are expected to improve symptoms, mobility and reduce hospitalizations for heart failure.

Intellia has developed a modular technology platform that supports in vivo and in vitro gene therapy. The focus of in vivo gene editing therapy research is on diseases caused by liver genes. Unlike some genomic drugs provided by engineered viruses, Intellia’s in vivo therapy uses lipid nanoparticles to achieve its goal. This difference is worth noting because the virus causes the immune system to produce antibodies against it, making any additional doses ineffective. Intellia’s Lipid Nanoparticle (LNP) platform does not have such problems, CEO John Leonard said on the conference call.

“One of the reasons we are excited about the LNP platform is that, in fact, you can readjust it,” he said. “This is a very important part of putting together a modular system, and a chemical-based approach rather than virological delivery.”

Leonard said that those who did not receive the maximum effective dose in clinical trials will be able to come back to receive higher doses. The treatment will be performed outside of clinical trials.

NTLA-2001 also shows early signs of a therapeutic advantage. ATTR’s treatment options include Alnylam Pharmaceuticals’ Onpattro, which became Obtained FDA approval for the first time Products based on a mechanism called RNA interference. This type of drug prevents genes from producing disease-causing proteins, and the drug has proven to reduce TTR by 80%. It is too early to know the durability of Intellia therapy, but early data suggests that NTLA-2001 can reduce TTR levels to potentially curative levels. In addition, compared with Onpattro, Intellia drugs are a one-time treatment and must be infused every three weeks.

The first phase of the NTLA-2001 study aims to recruit four groups of patients. Currently recruiting the third group, but Leonard said that if the company can choose from the three groups of tests to determine the recommended dose, the company has no obligation to start the fourth group. Chief Medical Officer David Lebwohl said that once the company has determined the dose, the therapy will begin the second part of the study, which will test the recommended dose in eight patients in a single group.

The ATTR data so far has given Intellia more confidence in NTLA-2002, which is a gene knockout therapy and is developing another rare disease, hereditary angioedema (HAE). Lebwohl said that HAE treatment candidates come from the same platform, so their safety is expected to be similar to ATTR therapy. He said that as the company approaches the start of research, the company will discuss the details of the NTLA-2002 clinical trial design.

In a research report, Luca Issi, a capital markets analyst at Royal Bank of Canada, described NTLA-2001 data as Intellia’s “home run.” The results of testing in a larger patient population and longer follow-up of these patients are necessary, but “we believe that data is a major risk-relief event of the platform, and we believe that HAE (NTLA-2002) can become Next one,” Isi wrote.

Intellia is collaborating with Regeneron Pharmaceutical to develop NTLA-2001, which began in 2016. The transaction requires partners to develop CRISPR-based therapies for the liver and improve the Intellia genome editing technology platform. The initial collaboration has been expanded to include hemophilia.

Intellia plans to present more data from the NTAL-2001 study at a medical or scientific conference later this year.

Graphics provided by Intellia Therapeutics

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