Shares of Intellia Therapeutics, Inc. (NTLA) were down in pre-market trading on Jan. 10 after the company announced a strategic reorganization to prioritize its portfolio of late-stage pipeline candidates and key anticipated milestones for 2025.As part of this portfolio reorganization, NTLA is planning to prioritize the development of its investigational in vivo genome-editing candidate, Nexiguran ziclumeran (nex-z, also known as NTLA-2001), which is being studied for two indications, ATTR amyloidosis with ...

Strategic Priorities and Milestones - Intellia Therapeutics announced its strategic priorities and key anticipated 2025 milestones, focusing on transforming patient lives through CRISPR-based therapies [1] - The company aims to transition from a late-stage development company to a commercial-ready organization by the end of 2026 [7] - Key priorities include driving clinical execution for NTLA-2002 and nex-z, advancing commercial readiness, and preparing for the first U S commercial launch [8][9] Pipeline Advancements - NTLA-2002 for Hereditary Angioedema (HAE): Phase 3 HAELO study enrollment to complete in the second half of 2025, with a Biologics License Application submission planned for the second half of 2026 [5] - Nex-z for Transthyretin (ATTR) Amyloidosis: Over 550 patients expected to be enrolled in the Phase 3 MAGNITUDE study by year-end 2025, with strong enrollment momentum [5][12] - NTLA-3001 discontinued to focus resources on NTLA-2002 and nex-z, resulting in a net workforce reduction of approximately 27% in 2025 [5][6] Financial and Operational Updates - Intellia ended Q4 2024 with approximately $862 million in cash, cash equivalents, and investments, providing a cash runway into the first half of 2027 [6] - The company expects to incur $8 million in charges related to the strategic reorganization in Q1 2025 [6] - Cost savings from workforce reduction and pipeline prioritization will support operations through the anticipated first commercial launch in the U S [5][6] Leadership Changes - Laura Sepp-Lorenzino, Ph D , Chief Scientific Officer, announced her retirement effective December 31, 2025, transitioning to a Senior Scientific Advisor role [6] - Birgit Schultes, Ph D , promoted to Executive Vice President and Chief Scientific Officer, effective January 13, 2025, bringing over 20 years of experience in drug development and biotechnology [6] Clinical Data and Presentations - Phase 2 data for NTLA-2002 presented at the 2024 ACAAI Scientific Meeting demonstrated potential to end chronic prophylaxis treatment with a one-time infusion [6] - Phase 1/2 data for NTLA-2002 and Phase 1 data for nex-z to be presented in 2025, including longer-term efficacy and safety measures [13] - First clinical evidence for nex-z presented at the 2024 AHA Scientific Sessions showed rapid, deep, and durable reductions in serum TTR, potentially halting or reversing disease progression [12] Commercial Readiness - Intellia plans to complete the buildout of its commercial leadership team by the second half of 2025 [13] - The company will expand medical education activities in HAE and ATTR amyloidosis and initiate pre-approval information exchange with payers in 2025 [13] - John Leonard, M D , President and CEO, will present a company overview at the 43rd Annual J P Morgan Healthcare Conference on January 13, 2025 [9]

Company Performance - Intellia Therapeutics, Inc. (NTLA) has experienced a significant decline in 2024, with shares dropping 60.4%, compared to the industry's decline of 13.7% [1] - The stock has underperformed relative to the sector and the S&P 500 Index over the past five months [1] Pipeline and Collaborations - NTLA has a promising pipeline of CRISPR-based therapies, including two in late-stage development: Nexiguran ziclumeran (nex-z) and NTLA-2002 [3][4] - Nex-z is designed to inactivate the transthyretin (TTR) gene to treat ATTR amyloidosis, with a collaboration agreement with Regeneron Pharmaceuticals for its development and commercialization [3] - NTLA-2002 aims to knock out the KLKB1 gene to control hereditary angioedema (HAE) attacks with a single dose [4] Clinical Data and Investor Sentiment - Data from a phase I study of nex-z showed a 90% mean serum TTR reduction at month 12, but safety data did not impress investors, leading to a selloff [5][7][16] - The phase I/II study of NTLA-2002 reported a 75% to 81% reduction in monthly attack rates for HAE patients [18] Financial Position - NTLA ended the third quarter with cash, cash equivalents, and marketable securities totaling $944.7 million, expected to fund operations into late 2026 [9] - The company's shares currently trade at a price/book ratio of 1.28x, lower than the industry average of 3.47 [10] Market Outlook - The Zacks Consensus Estimate for NTLA's 2024 loss per share has narrowed to $5.31, indicating some adjustments in market expectations [21] - Investors remain skeptical about the recent data from NTLA's therapies, which may impact the company's future performance [23]

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]

Core Insights - The U.S. FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to Intellia Therapeutics' investigational therapy nexiguran ziclumeran (nex-z, also known as NTLA-2001) for treating hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN) [1][2] - Nex-z is designed as a single-dose CRISPR-based therapy aimed at inactivating the TTR gene to prevent TTR protein production, potentially halting and reversing the disease [1][4] - This RMAT designation is the third special regulatory designation received by Intellia for nex-z, which also holds Orphan Drug Designation from the FDA and the European Commission [3] Company Overview - Intellia Therapeutics is a clinical-stage gene editing company focused on CRISPR-based therapies, with programs that enable precise editing of disease-causing genes in vivo and ex vivo [6] - The company collaborates with Regeneron for the development and commercialization of nex-z as part of a multi-target initiative [1][4] Disease Context - ATTR amyloidosis is a rare and progressive disease caused by mutations in the TTR gene, leading to the production of misfolded TTR proteins that accumulate and cause serious complications [5] - There are approximately 50,000 individuals globally with hereditary ATTR amyloidosis and between 200,000 to 500,000 with wild-type ATTR amyloidosis, with no known cure currently available [5]

Shares of biotech Intellia Therapeutics (NTLA 5.18%) are down by around 33% over the past 30 days, amid the publication of some new data from an early stage clinical trial on Nov. 16 and its third-quarter earnings on Nov. 7.Usually, updates like those two would act as positive catalysts for a stock, assuming there was good news to share.In this case, there wasn't exactly any bad news, but the stock is clearly still smarting from the damage in October, when some clinical results from its gene editing program ...

Core Insights - Intellia Therapeutics announced positive clinical data from the Phase 1 trial of nexiguran ziclumeran (nex-z) for treating transthyretin (ATTR) amyloidosis, indicating that significant reductions in serum TTR levels may correlate with clinical benefits in patients [1][3][15] ATTR-CM Arm Results - A single dose of nex-z resulted in a mean serum TTR reduction of 90% at month 12, with a mean residual serum TTR concentration of 17 µg/mL [4] - Patients showed evidence of disease stabilization or improvement across multiple cardiac disease progression markers at month 12, despite a high proportion of advanced heart failure cases [4][5] - 92% of patients demonstrated stability or improvement in their NYHA functional classification, with all patients classified as NYHA Class III at baseline showing improvement or no change at month 12 [5] ATTRv-PN Arm Results - In patients receiving a dose of 0.3 mg/kg or higher, the mean serum TTR reduction was 91% at month 12, with a mean residual serum TTR concentration of 20 µg/mL [8] - Favorable trends indicating stability or improvement were observed in clinical measures such as Neuropathy Impairment Score (NIS) and modified Neuropathy Impairment Score (mNIS+7) [8][9] Safety Profile - Nex-z was generally well tolerated, with infusion-related reactions being the most commonly reported treatment-related adverse events, which were predominantly mild to moderate [7][10] Future Studies - The ongoing Phase 3 MAGNITUDE study aims to evaluate the efficacy and safety of nex-z in approximately 765 patients with ATTR-CM, focusing on cardiovascular-related mortality and events [13] - The MAGNITUDE-2 study will assess the efficacy and safety of nex-z in 50 adults with ATTRv-PN, with primary endpoints including changes in modified Neuropathy Impairment Score +7 [14]

Brendan, a Pennsylvanian by birth:-Completed a Ph.D. at Stanford University in the field of organic synthesis (2009). -Worked for a major pharmaceutical company (Merck, 2009-2013).-Worked in biotech including start-ups prior to co-founding 1200 Pharma at the California Institute of Technology (Caltech, 2016).-Became the first employee of 1200 Pharma as it spun out of Caltech garnering major investment (into the 8 figures)-Remains an avid investor, focused on market trends and especially biotechnology stocks ...

Core Insights - Intellia Therapeutics reported a narrower loss of $1.34 per share for Q3 2024, compared to the Zacks Consensus Estimate of a loss of $1.37 and a loss of $1.38 in the same quarter last year [1] - Total revenues for the quarter were $9.1 million, down from $12 million year-over-year, but exceeded the Zacks Consensus Estimate of $8 million [1][2] - The decline in revenues was attributed to reduced income from the AvenCell license and collaboration agreement [2] Financial Performance - Research and development expenses increased by 8.5% year-over-year to $123.4 million, driven by advancements in lead pipeline programs [3] - General and administrative expenses rose by approximately 3.7% year-over-year to $30.5 million, primarily due to increased stock-based compensation [3] - As of September 30, 2024, the company had cash, cash equivalents, and marketable securities totaling $944.7 million, slightly up from $939.9 million as of June 30, 2024 [4] Pipeline Developments - Intellia is collaborating with Regeneron Pharmaceuticals on the investigational in vivo genome-editing candidate, Nexiguran ziclumeran (nex-z), which is currently in a Phase III study for ATTR amyloidosis with cardiomyopathy [5][6] - The FDA has cleared the IND application for the pivotal Phase III MAGNITUDE-2 study for treating hereditary ATTR amyloidosis with polyneuropathy, with patient enrollment expected to begin outside the U.S. by the end of 2024 [7] - The company has initiated the pivotal Phase III HAELO study for NTLA-2002, targeting hereditary angioedema, with the primary endpoint focused on the change in the number of HAE attacks [8] - Intellia plans to dose the first patient in a Phase I/II study for NTLA-3001, aimed at treating alpha-1 antitrypsin deficiency associated lung disease, by the end of 2024 [9] Market Performance - Intellia's shares have declined by 47.6% year-to-date, contrasting with a 2.4% decline in the broader industry [2] - The company currently holds a Zacks Rank of 2 (Buy) [10]

Financing and Cash Position - The company has raised approximately $2,758.3 million to fund operations through various financing methods since inception until September 30, 2024[95]. - Net cash provided by financing activities was $183.4 million during the nine months ended September 30, 2024, including $176.9 million from at-the-market offerings[149]. - As of September 30, 2024, the company had $944.7 million in cash, cash equivalents, and marketable securities[135]. - The company expects to fund ongoing operating expenses and capital requirements into late 2026 based on current cash and collaboration funding[142]. - The company raised an aggregate of $2,758.3 million since inception through various financing methods, including public offerings and collaboration agreements[135]. - The company has $249.1 million in shares of common stock remaining eligible for sale under the amended 2022 Sale Agreement[138]. Clinical Trials and Development - The pivotal Phase 3 MAGNITUDE trial for NTLA-2001 is currently enrolling patients, with a 2:1 randomization of NTLA-2001 to placebo, and the first patients were dosed in March 2024[99]. - The MAGNITUDE-2 trial for hereditary ATTR amyloidosis (ATTRv-PN) is set to evaluate 50 adults, with primary endpoints including change in modified Neuropathy Impairment Score +7 at month 18[100]. - NTLA-2002 has shown a 98% mean reduction in monthly HAE attack rate compared to baseline in a Phase 1 study, with eight out of ten patients remaining completely attack-free for over 18 months[107]. - The company plans to submit a biologics license application for NTLA-2002 in 2026 following the ongoing Phase 3 study[104]. - The Phase 1/2 trial of NTLA-2002 met its primary efficacy and all secondary endpoints, leading to the selection of a 50 mg dose for further evaluation[106]. - The company is advancing multiple ex vivo programs for immuno-oncology and autoimmune diseases, alongside its in vivo candidates[96]. - The company is focused on developing curative CRISPR/Cas9-based medicines and expanding its gene editing capabilities with proprietary technologies[92]. - The company has received FDA clearance for the IND application to initiate the MAGNITUDE-2 trial for ATTRv-PN[100]. - The company is the clinical and commercial lead party in a co-development arrangement with Regeneron for the ATTR program, sharing approximately 25% of worldwide development costs and profits[102]. - In the Phase 1/2 study of NTLA-2002, 8 out of 11 patients in the 50 mg arm remained attack-free for 16 weeks after a single dose, indicating a potential functional cure for HAE[109]. - NTLA-3001 is set to initiate a first-in-human study by year-end 2024, with expectations to dose the first patient in a Phase 1/2 study involving up to 30 patients[111]. - The median reduction in serum TTR was 90% at day 28 after redosing with NTLA-2001, indicating a significant pharmacodynamic effect[112]. Financial Performance - Collaboration revenue decreased by $2.9 million to $9.1 million for the three months ended September 30, 2024, primarily due to a reduction in revenue under the AvenCell license agreement[121]. - Research and development expenses increased by $9.7 million to $123.4 million for the three months ended September 30, 2024, compared to the same period in 2023[124]. - General and administrative expenses rose by $1.1 million to $30.5 million for the three months ended September 30, 2024, mainly due to an increase in stock-based compensation[125]. - Collaboration revenue increased by $6.8 million to $45.0 million for the nine months ended September 30, 2024, compared to $38.2 million in the same period of 2023[129]. - Operating loss for the three months ended September 30, 2024, was $144.8 million, compared to $131.1 million for the same period in 2023, reflecting an increase of $13.7 million[122]. - Total operating expenses for the three months ended September 30, 2024, were $153.9 million, an increase of $10.8 million from $143.1 million in the same period of 2023[122]. - Other income, net increased by $0.2 million to $9.1 million for the three months ended September 30, 2024, primarily due to changes in equity method losses and fair value of investments[126]. - Research and development expenses increased by $23.3 million to $349.4 million for the nine months ended September 30, 2024, compared to $326.1 million for the same period in 2023, representing a 7% increase[130]. - External development expenses for NTLA-2001 rose by $11.7 million (30%) to $51.2 million, while NTLA-2002 expenses increased by $14.7 million (90%) to $31.1 million[131][132]. - General and administrative expenses increased by $5.9 million to $93.4 million during the nine months ended September 30, 2024, primarily due to a $6.3 million increase in stock-based compensation[133]. - Net cash used in operating activities was $263.7 million for the nine months ended September 30, 2024, compared to $301.0 million for the same period in 2023[144][146]. - The company anticipates an increase in expenses for the remainder of 2024 as it continues to develop clinical programs[140].