Intellia hits a 'home run' with gene-editing results, setting up entire field for a grand slam

Intellia’s gene-editing results “decisively exceeded” analyst expectations, launching the rest of the field into the spotlight overnight and maybe, just maybe, providing some fodder for the FDA to lighten up on its resistance to hosting gene-editing trials in the U.S. 

Shares of the Cambridge, Massachusetts-based biotech gained more than 55% Monday, rising to $133.43 at close.

The results were a pretty big deal: Intellia and partner Regeneron showed for the first time that gene editing can work in a human. NTLA-2001 reduced serum levels of transthyretin, a key biomarker in the rare disease transthyretin (ATTR) amyloidosis, by 87%, besting standard-of-care therapies that typically reach 80%.

Other companies in the gene-editing game saw a spike in the stock market, too, such as CRISPR Therapeutics, which shot up from around $138 to a high of $156 Monday.

Stifel predicts the Intellia effect will boost Precision Biosciences and Beam Therapeutics, too, and could even convince the FDA to be more open to hosting gene-editing trials in the U.S.

So far, only Sangamo Therapeutics has managed to host a trial here for a gene therapy that tackles two types of the rare genetic disease mucopolysaccharidosis. Intellia’s NTLA-2001 trial was hosted in New Zealand and London.

RELATED: With first-in-human trial results, Intellia shows the world that gene editing has arrived

Investor expectations were high for NTLA-2001, and analyst after analyst said the results blew away their predictions. The recorded serum reduction shows the therapy could become a blockbuster, according to SVB Leerink Analyst Mani Foroohar, M.D.

NTLA-2001 also appears to have reached the liver as attended, validating Intellia’s entire platform that relies on this delivery mechanism for editing genes, according to JMP Securities.

“This result surpassed our expectations and achieved our ‘home run’ scenario,” wrote JMP’s Silvan Tuerkcan, Ph.D.

Intellia was surprised at the strength of the data as well; David Lebwohl, M.D., Intellia's chief medical officer, told Fierce Biotech that the serum reduction was “beyond what we expected.”

ATTR amyloidosis is a rare and fatal disease that occurs in people born with TTR gene mutations, which cause the liver to produce abnormal, often misfolded TTR proteins. The damaged proteins, which in a healthy form help carry thyroid hormone and vitamin A in the blood, build up in the body, causing a host of problems to the nervous system, heart and other organs.

NTLA-2001 is currently only being trialed in the polyneuropathy subtype of the disease, which shows up as nerve damage. But Intellia wants to expand into the two other subtypes, wild type and the cardiomyopathy manifestation.

RELATED: In conversation with John Leonard, CEO of Intellia

Intellia hopes the results will ultimately stick, offering patients a one-and-done treatment. Analysts are already saying they have what it takes to go up against the existing market holders, mainly Alnylam’s Onpattro.

Chardan Research said the data show that NTLA-2001 has the potential to become a “functional cure” for ATTR amyloidosis.

Leerink's Foroohar said the current standard-of-care therapies are expensive and have “onerous chronic delivery schedules,” meaning Intellia’s therapy can easily slip in and rule the market. Other market placeholders include Ionis’ Tegsedi and Pfizer’s Vyndaqel, which is approved in the U.S. for the cardiomyopathy type of the disease only. Vyndaqel is approved for the polyneuropathy form in several other countries.

Intellia CEO John Leonard headshot
John Leonard, M.D. (Intellia)

As with any new drug that companies want to bring to the U.S. market, price was top of mind for analysts, who dug for details on a Monday conference call. Intellia is on new turf here, since the company is the first to provide proof-of-concept gene-editing results—and President and CEO John Leonard, M.D., was not interested in speculating on where they may land on pricing.

“We've never offered an approach or a price. That is a strawman put up by people who do that at their own peril,” Leonard said. “So I would say that we're going to be in an excellent position to bring not only medical value to patients, but I fully expect it will bring value to the healthcare system and that's our objective here.”

RELATED: The next generation of gene therapy for rare diseases forges ahead as developers weather hurdles

Jefferies noted the pledge to offer competitive pricing but said Intellia could “have a high ceiling” for that ultimate number, given the one-time treatment could mean cost savings over time for patients who can ditch chronic therapy.

Intellia saw a good response on the high dose tested in the trial and only low-grade adverse events. JMP believes there's room to move up the dose in later studies, which is exactly what the company is planning. Once those data come in, NTLA-2001 will move into pivotal studies. Patients who received the lower dose in the earlier trial, who did see some serum reductions, could be re-dosed to get the full effect, JMP noted.

Attention now shifts to the rest of Intellia’s portfolio, which includes NTLA-2002 in hereditary angioedema and NTLA-5001 in acute myeloid leukemia. Jefferies is also watching for Intellia to name a couple more candidates by the end of the year and in the first half of 2022.

Intellia has a few questions to answer, but one thing is for sure: Investors are hungry for any tidbit of information they can provide as NTLA-2001 moves through the clinic.