• First-ever clinical data demonstrating redosing with an investigational in vivo CRISPR-based therapy
  • Follow-on dosing with a 55 mg dose of NTLA-2001 led to a 90% median reduction in serum TTR at day 28 in the three patients who previously received the lowest dose in the Phase 1 dose-escalation study
  • 55 mg follow-on dose was well tolerated across all patients
  • While redosing is not planned for the NTLA-2001 program in transthyretin (ATTR) amyloidosis, a redosing option could be an important advantage of Intellia’s non-viral, lipid nanoparticle (LNP)-based delivery platform for future investigational therapies where a target additive effect is desired

CAMBRIDGE, MA, USA I June 25, 2024 I Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today presented new data demonstrating for the first time the potential for redosing with an investigational, in vivo CRISPR/Cas9 genome editing therapy. These data from the ongoing Phase 1 study of NTLA-2001, a single-dose treatment in development for transthyretin (ATTR) amyloidosis, were presented at the Peripheral Nerve Society Annual Meeting, taking place June 22–25 in Montreal, Canada.

“Today’s data showcase an exciting new platform advancement for Intellia and the field of gene editing. For the first time ever, we demonstrated that redosing with CRISPR, utilizing our proprietary, non-viral LNP-based delivery platform, enabled an additive pharmacodynamic effect on the target protein,” said Intellia President and Chief Executive Officer John Leonard, M.D. “While redosing is not planned for the NTLA-2001 program for the treatment of transthyretin amyloidosis, part of our commitment to patients enrolled in the dose-escalation portion of the Phase 1 study was to provide them with the opportunity to receive the therapeutic dose selected if they did not reach the target protein reduction level. These data provide platform proof-of-concept that we can re-dose, if necessary, enabling us to pursue treatment of other diseases where patients might need more than one dose to reach the desired therapeutic effect.”

NTLA-2001 is currently being evaluated in patients with either ATTR amyloidosis with cardiomyopathy (ATTR-CM) or hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). Development and commercialization of NTLA-2001 is led by Intellia as part of a multi-target collaboration with Regeneron. Data from the Phase 1 trial has demonstrated that a one-time 55 mg dose of NTLA-2001 led to consistent, deep and durable reduction of serum TTR protein levels. This 55 mg dose was selected for further evaluation in the actively enrolling Phase 3 MAGNITUDE trial for ATTR-CM and the planned Phase 3 trial for ATTRv-PN.

In the Phase 1 trial, the three initial patients enrolled in the dose-escalation portion received a 0.1 mg/kg dose of NTLA-2001, which led to a 52% median reduction in serum TTR by day 28. As expected, the 0.1 mg/kg dose resulted in lower-than-targeted serum TTR reduction. These patients were offered the opportunity to receive a follow-on dose of NTLA-2001 at the completion of the protocol-specified two years of observation. All three patients subsequently received a 55 mg dose, which led to the target pharmacodynamic effect and a 90% median reduction in serum TTR by day 28. The corresponding reduction from original baseline levels was a 95% median reduction in serum TTR. NTLA-2001 was generally well tolerated across all patients after receiving the follow-on dose. One of the three patients experienced a mild infusion-related reaction with the 55 mg dose. Safety and pharmacodynamics of the NTLA-2001 redosing were consistent with those observed after a single 55 mg dose. Further, favorable safety and tolerability continues to be observed, with patient follow-up beyond three years for the earliest dosed patient.

The ability to re-dose is a key advantage of Intellia’s non-viral, lipid nanoparticle (LNP)-based delivery platform. These results are the first-ever clinical data demonstrating redosing with a CRISPR-based medicine, enabling the potential treatment of diseases where a target additive pharmacodynamic effect is desired.

About NTLA-2001
Based on Nobel Prize-winning CRISPR/Cas9 technology, NTLA-2001 has the potential to become the first one-time treatment for transthyretin (ATTR) amyloidosis. NTLA-2001 is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. NTLA-2001 is the first investigational CRISPR therapy to be administered systemically to edit genes inside the human body. Interim Phase 1 clinical data showed the administration of NTLA-2001 led to consistent, deep and long-lasting TTR reduction. Intellia leads development and commercialization of NTLA-2001 as part of a multi-target discovery, development and commercialization collaboration with Regeneron.

About Transthyretin (ATTR) Amyloidosis
Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis. There is no known cure for ATTR amyloidosis and currently available medications are limited to slowing accumulation of misfolded TTR protein.

About Intellia Therapeutics
Intellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. The company’s in vivo programs use CRISPR to enable precise editing of disease-causing genes directly inside the human body. Intellia’s ex vivo programs use CRISPR to engineer human cells outside the body for the treatment of cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its people, is helping set the standard for a new class of medicine. To harness the full potential of gene editing, Intellia continues to expand the capabilities of its CRISPR-based platform with novel editing and delivery technologies. Learn more at intelliatx.com and follow us @intelliatx.

SOURCE: Intellia Therapeutics