Intellia Therapeutics

Intellia reported $7.7 million in second-quarter collaboration revenue and submitted its US filing for lonvo-z in hereditary angioedema. Intellia ended the quarter with a net loss of $106 million and $628 million in cash and cash equivalents.

Why it matters: Intellia submitted US filings for lonvo-z (in hereditary angioedema), which we assign an 80% probability of approval. We think it could reach the market in 2027 and achieve $1 billion in sales by the end of our 10-year forecast. If approved, lonvo-z would represent the first widely commercialized in vivo CRISPR therapy. We think successful commercialization would help validate Intellia's delivery and editing platform. Intellia and Regeneron's recent discovery of a genetic marker linked to the most severe liver safety events for their nex-z gene editing treatment for ATTR amyloidosis could help reframe this overhang from a potential platformwide safety concern to a more defined and screenable patient-selection issue.

The bottom line: We maintain no-moat Intellia's fair value estimate of $27 per share. We view the shares as significantly undervalued, trading in 5-star territory about 55% below our valuation. In our view, the market is underappreciating the commercial potential of lonvo-z as the first one-time treatment for HAE and is assigning little value to pipeline upside ahead of additional clinical data and regulatory milestones. Lonvo-z is wholly owned by Intellia, unlike nex-z, allowing the company to capture the full economics of what could become the first commercialized in vivo CRISPR therapy. We believe the market is underestimating demand for a one-time treatment option in HAE, which could support strong uptake and pricing power relative to chronic therapies. We continue to assign a 15% probability of approval to nex-z, pending additional clinical data. Positive results could support a higher probability of success and provide upside to our valuation.

Our Very High Uncertainty Rating reflects regulatory risks for Intellia's pipeline, plus payer reimbursement and commercial uptake uncertainty.

We maintain Intellia's fair value estimate of $27 per share.

In March 2025, the US Food and Drug Administration lifted Intellia's clinical hold on its gene therapy trial for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) treated with nex-z after previous reports of serious liver toxicity that led to a patient death in the trial. As part of aligning with the FDA on new trial measures, Intellia will enhance liver lab monitoring and exclude patients with certain liver abnormalities or recent cardiovascular instability.

Nevertheless, the cause of the liver toxicity remains unclear, and we assign nex-z a 15% base-case probability of approval. Even if nex-z were to receive approval, it may face commercial headwinds due to its anticipated $1 million or higher price. Intellia is hoping its long-lasting gene-editing treatment will be a better alternative to other ATTR-CM medicines that slow disease progression, such as BridgeBio's oral Attruby (approved in November 2024) and Alnylam Pharmaceuticals' injectable Amvuttra (approved in March 2025). Growing competition in the ATTR-CM field creates a high standard for Intellia, especially for its safety profile. Strong uptake of BridgeBio’s Attruby and Alnylam’s Amvuttra and their high safety and efficacy heightens competition for Intellia.

Nex-z is part of a co-development and co-promotion agreement with narrow-moat Regeneron. Regeneron shares in 25% of worldwide development costs and commercial profits for the ATTR program. We like that Intellia will retain 75% of economic profits of Nex-z, if approved, and the company also has the expertise and financial support of Regeneron to offset some of the development costs.

In January 2025, management made the strategic decision to prioritize its two late-stage programs, Lonvo-z and Nex-z to focus on near-term value creation. As a result, it discontinued NTLA-3001 (a gene editing treatment for lung disease) and reduced its workforce by approximately 27%.

While the company does not yet have approved products, it provides long-term investors with pure play exposure to novel gene editing technology to treat severe genetic diseases. Intellia's pipeline candidates span a diverse range of diseases with very high unmet needs, which will likely lead to pricing power if its therapies receive approval.

Intellia submitted US filings for Lonvo-z (in hereditary angioedema), to which we assign an 80% probability of approval. We think it could reach the market in 2027 and achieve $1 billion in sales by the end of our 10-year forecast. If approved, Lonvo-z would represent the first widely commercialized in vivo CRISPR therapy. We think successful commercialization would help validate Intellia's delivery and editing platform

Given Intellia's Very High Morningstar Uncertainty Rating and range of potential outcomes due to its early stage pipeline, we use an 11% cost of equity. This is higher than our typical 9% cost of equity for other biotech companies under our coverage.

We assign Intellia Therapeutics a no-moat Morningstar Economic Moat Rating. Intellia is focused on developing and commercializing novel therapies to treat severe, genetic diseases, and its lead candidate, Lonvo-z for hereditary angioedema (HAE), is under US regulatory review. We think the company has the funding and technological capabilities to potentially bring several pipeline programs to market. However, we see a very high level of uncertainty related to regulatory approvals for the company’s portfolio and a range of potential outcomes.

The narrow moat definition requires excess normalized returns to more likely than not be positive 10 years from now, with no substantial threat of major value destruction. Our Very High Morningstar Uncertainty Rating for Intellia reflects the substantial threat of major value destruction facing this clinical-stage biotech.

Biotech moats typically stem from intangible assets, namely patents and regulatory exclusivity on approved drugs with pricing power. With no marketed drugs, Intellia does not yet possess an economic moat. We are closely watching Intellia’s pipeline candidates for signs of competitive advantages. Multiple pipeline opportunities span rare diseases with high unmet medical needs, which could support pricing power, but we await additional trial data to gauge the company’s true commercial potential.

HAE and ATTR amyloidosis are areas of high, critical need where genetic therapies could achieve high efficacy and command strong pricing power. Both markets are already served by chronic therapies, so Intellia’s edge would come from a one-time treatment offering deeper, lasting benefit and freeing patients from repeat dosing.

Intellia’s proprietary platform specializes in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing, which precisely cuts DNA to disrupt, delete, correct, and insert genes to treat genetically defined diseases. Crispr/Cas9-based technologies have led to a new class of therapies, which are well suited for targeting rare diseases or other disorders that are caused by genetic mutation or unwanted gene expression. Intellia has leveraged its expertise in Crispr/Cas9 gene editing to advance a pipeline focused on in vivo therapies for diseases with high unmet medical needs.

In vivo programs use intravenously administered CRISPR, with Intellia’s proprietary lipid nanoparticle delivery technology enabling precise editing of disease-causing genes directly within target tissues. Following a January 2025 restructuring, Intellia deprioritized its ex vivo work, which addressed immune-oncology and autoimmune disease by engineering cells outside the body, to concentrate resources on its two late-stage in vivo programs, Lonvo-z and Nex-z.

Nex-z is for transthyretin amyloidosis (ATTR) and Lonvo-z is for HAE, the first CRISPR/Cas9 based therapies administered systemically via intravenous infusion for precision gene editing in humans. Nex-z is part of a co-development and co-promotion agreement with narrow moat Regeneron, under which Intellia leads clinical and commercial efforts while Regeneron shares 25% of worldwide development costs and commercial profits. We like that Intellia retains 75% of Nex-z economic profits if approved, benefiting from Regeneron’s expertise and financial support, while Lonvo-z is wholly owned by Intellia.

Intellia targets in vivo liver indications using well validated targets and predictive biomarkers for ATTR amyloidosis and HAE. It uses a gene knockout approach paired with its proprietary lipid nanoparticle delivery system to remove unwanted proteins. Intellia also has early stage candidates evaluating restoration of native protein in hemophilia B and other undisclosed indications.

ATTR amyloidosis is a progressive, fatal disease marked by abnormal buildup of misfolded transthyretin protein in the body's organs and tissues. Intellia and narrow-moat Regeneron announced positive phase 1 data showing Nex-z achieved a mean reduction in transthyretin, the disease-causing protein, of about 90% at 12 months. The companies are evaluating Nex-z in phase 3 trials in ATTR amyloidosis with polyneuropathy and with cardiomyopathy.

In October 2025, Intellia paused both Nex-z trials after a patient treated for the cardiomyopathy indication was hospitalized and later died of severe liver damage. As a result, we lowered our probability of approval for both Nex-z trials to 15% from 40% in our base-case scenario.

Intellia’s foundational CRISPR/Cas9 rights come from a 2014 Caribou Biosciences

sublicense, which stems from the University of California Berkeley and Vienna estate, rather than a direct license from co-inventor Emmanuelle Charpentier. Charpentier instead allocated her personal, direct allocations to CRISPR Therapeutics and ERS Genomics. For investors, the bigger risk is the unresolved Broad Institute patent dispute. The Patent Trial and Appeal Board ruled for Broad in February 2022, the Federal Circuit vacated that ruling in May 2025, and the board again favored Broad in March 2026, with appeals still possible. If Broad ultimately prevails, Intellia would likely need a separate license to commercialize its therapies, adding cost and uncertainty to its already speculative path to market. Intellia and other gene editing companies may need to separately license Broad’s patents, but Intellia also holds its own intellectual property, including improvements to Crispr/Cas9, delivery methods and methods of treating disease using Crispr/Cas9 genome editing. Intellia’s internally developed patents are not expected to expire before 2036.

Intellia's partnerships allow it to receive milestones and economic benefits from drug candidate progression while offsetting some of the clinical development costs.

Intellia's Crispr/Cas9 platform has the potential to develop highly efficacious and curative treatments for rare, genetic diseases with high unmet needs, which will likely lead to pricing power if approved.

Intellia has a lengthy patent protection for its developing pipeline as its patents do not expire until 2036.

Intellia's pipeline is largely in the early stages of development and years away from potentially receiving approval.

While Intellia is a leading clinical-stage gene editing company, there are many other companies also researching and investing in these novel medicines, which could lead to competitive pressure in the future.

Intellia's Very High Uncertainty Rating highlights the risks associated with its early-stage pipeline and the range of potential outcomes for the company.