NTLA Up as FDA Grants RMAT Status to Genome-Editing Therapy

Regulatory Designation and Impact - The FDA granted the Regenerative Medicine Advanced Therapy (RMAT) designation to Intellia Therapeutics' investigational in vivo genome-editing candidate, Nexiguran ziclumeran (nex-z, also known as NTLA-2001), for the treatment of hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN) [1] - The RMAT designation facilitates early interactions with the FDA, including discussions on surrogate or intermediate endpoints, and supports accelerated approval and potential priority review of the biologics license application (BLA) [2] - Shares of Intellia rose 3.4% following the announcement, although the stock has declined 51.6% year-to-date compared to the industry's 9% decline [3] Clinical Development and Collaborations - Interim data from a phase I study showed that a one-time treatment with nex-z led to rapid, deep, and durable TTR reduction, which is likely to halt and potentially reverse the disease [4] - Intellia has a co-development and co-promotion agreement with Regeneron Pharmaceuticals for nex-z, with Regeneron sharing 25% of the development costs and commercial profits [5] - The FDA cleared Intellia's investigational new drug (IND) application for the pivotal phase III MAGNITUDE-2 study, which will evaluate nex-z for ATTRv-PN, with patient enrollment expected to begin outside the U.S. by the end of 2024 [6] Ongoing Studies and Future Prospects - The phase III MAGNITUDE study is currently evaluating the safety and efficacy of nex-z in patients with ATTR amyloidosis with cardiomyopathy (ATTRv-CM), with enrollment ongoing [7] - Positive data from the MAGNITUDE study could enable global regulatory filings for nex-z, making its successful development crucial for Intellia [7] Industry Context and Peer Performance - Intellia currently holds a Zacks Rank 3 (Hold), while other biotech companies like Spero Therapeutics (SPRO) and Castle Biosciences (CSTL) are ranked 1 (Strong Buy) [8] - Spero Therapeutics' 2024 loss per share estimates narrowed from $1.59 to$1.13, and its 2025 estimates narrowed from $1.54 to$0.54, with shares declining 21.7% year-to-date [9] - Castle Biosciences' 2024 loss per share estimates narrowed from $0.58 to$0.08, and its 2025 estimates narrowed from $2.13 to$1.88, with shares surging 36.8% year-to-date [10] - Castle Biosciences has consistently beaten earnings estimates in the past four quarters, with an average surprise of 172.72% [11]