The Predictive Value of Carotid Ultrasonography With Cardiovascular Risk Factors—A “SPIDER” Promoting Atherosclerosis

Creating The World's First CRISPR Medicine, For Sickle Cell Disease

When Vijay Sankaran was an MD-PhD student at Harvard Medical School in the mid-2000s, one of his first clinical encounters was with a 24-year-old patient whose sickle cell disease left them with almost weekly pain episodes.

"The encounter made me wonder, couldn't we do more for these patients?" said Sankaran, who is now the HMS Jan Ellen Paradise, MD Professor of Pediatrics at Boston Children's Hospital.

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As a budding hematologist, Sankaran knew all too well that people with sickle cell disease — marked by malformed, sickle-shaped red blood cells that can aggregate and block small vessels — experience excruciating pain crises, tissue and organ damage, and shortened life expectancy.

He also understood that the only treatment available at the time was hydroxyurea, which reduces sickling but isn't effective in all patients and can cause side effects. The only chance at a cure was to undergo a bone marrow transplant, available to only a small percentage of patients because it carries significant risks and requires a well-matched donor.

Sankaran's rotations through the hematology clinic made him want to change the story of the disease, both at the bedside as a soon-to-be physician and by joining the laboratory of HMS alumnus Stuart H. Orkin, the HMS David G. Nathan Distinguished Professor of Pediatrics at Boston Children's and Dana-Farber Cancer Institute.

In 2008, Orkin, Sankaran, and colleagues achieved their vision by identifying a new therapeutic target for sickle cell disease.

In December 2023, through the development efforts of CRISPR Therapeutics and Vertex Pharmaceuticals, their decades-long endeavor reached fruition in the form of a new treatment, CASGEVY, approved by the U.S. Food and Drug Administration.

The decision has ushered in a new era for sickle cell disease treatment — and marked the world's first approval of a medicine based on CRISPR/Cas9 gene-editing technology.

A foundation for the first gene-editing medicine

By the time Sankaran joined the federally supported Orkin Lab, Orkin had been illuminating the underlying mechanisms of red blood cell development and function and related hematological disorders for decades.

"Over the last 40 years, Stu has been a pioneer," said HMS alumnus David Altshuler, executive vice president and chief scientific officer at Vertex and senior lecturer on genetics, part-time, at HMS, who oversaw the development of CASGEVY. "Through his work, we've come to understand how red blood cells work, how they develop in the body, and, particularly, how mutations lead to sickle cell disease."

Sickle cell disease stems from a mutation in the gene that makes hemoglobin, the protein in red blood cells that carries oxygen throughout the body. Orkin's team and others revealed that hemoglobin has two forms — fetal and adult — and that only the adult form is affected by sickle cell mutations, while the fetal form functions normally. However, shortly after birth, fetal hemoglobin production is turned off in the body, while adult hemoglobin production takes over.

Orkin had been investigating whether it was possible to switch fetal hemoglobin back on to treat sickle cell disease, but progress had stalled. Then, with help from Sankaran, patient samples from the National Institutes of Health, and a team in Sardinia, Italy, advances in genome-wide association studies revealed the gene that would hold the ticket: BCL11A.

Sankaran and Orkin showed that BCL11A suppresses production of fetal hemoglobin. Their landmark publication in Science kicked off a new era for sickle cell disease research.

Just three years later, in 2011, Orkin and others in his group showed that removing BCL11A from developing red blood cells in a mouse model of sickle cell disease turned on fetal hemoglobin production and cured the mice. This laid the foundation for clinical trials.

In 2013, another hematology fellow who joined the Orkin laboratory, Daniel Bauer — now the HMS Donald S. Fredrickson, MD Associate Professor of Pediatrics at Boston Children's — identified a DNA sequence in BCL11A that, when removed, drastically reduced the gene's activity.

Then CRISPR/Cas9 gene-editing technology swept onto the scene, and Bauer, Orkin, and colleagues identified a single DNA cut that could impair BCL11A activity.

But a steep climb remained to transform this discovery into a safe and effective gene therapy for patients. Appreciating both the difficulty and the importance of such work, the researchers and their home institutions made the intellectual property available to companies through nonexclusive licensing.

Bringing the first genetic medicines to patients

Altshuler decided in 2015 to leave academia after 25 years, including 15 years as HMS professor of genetics and of medicine, to join Vertex full-time. He was motivated to contribute to the paradigm shift happening in genetic medicine — particularly the translation of biological insights into therapies for patients.

"My mind moved on from discovery to 'how are we going to make therapies?'" he explained. "We were looking for new programs where we could make a transformative medicine for people with a serious disease."

Altshuler had followed the work of the Orkin Lab for many years, and he had taught Sankaran in the classroom. On day one at Vertex, he knew that he wanted to work on BCL11A.

We were looking for new programs where we could make a transformative medicine for people with a serious disease.

David Altshuler

Vertex executive vice president and chief scientific officer; HMS senior lecturer on genetics, part-time

Over the next nine years, Altshuler oversaw further research and development of the experimental therapy through a plethora of preclinical and clinical studies led by CRISPR Therapeutics and Vertex.

In clinical trials, the therapy eliminated small-vessel blockages, known as vaso-occlusive or sickle cell crises, for virtually all patients.

Today, CASGEVY is approved for use in patients with sickle cell disease in the United States and multiple countries in Europe and the Middle East.

"It's an amazing gift to have been able to play a role in such a thing," said Altshuler.

The tale continues

Vertex is working to secure approvals in additional countries, and it takes time after such approvals for treatments to actually become available to patients. Altshuler estimates it will take another 5 to 10 years to provide maximum access.

Plus, researchers including Orkin, Sankaran, and those at Vertex continue to conduct research to make sickle cell treatment more effective, more efficient, and appropriate for even more patients. Right now, only a subset of patients qualify for CASGEVY, mainly because it requires a bone marrow transplant and access to well-resourced health care facilities. Access is also limited by treatment cost. The current treatment also does not reverse permanent damage previously wrought on the body by the disease.

"It's the beginning of a long journey," said Altshuler. "We will keep working to make better therapies until we can help all patients with this disease around the world."

For his part, Sankaran has been thrilled to see a new option for patients and to be part of what he hopes is a growing trend of academia-industry partnerships that shorten the time and raise the success rates of bringing lab discoveries to the clinic.

"I'm excited about what's ahead, because as somebody who spends their time largely in the laboratory, I see things happening — fundamental discoveries — that hopefully will also start to impact the kind of therapies that industry can test in patients," he said.

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Your Next Pet Could Be A Glowing Rabbit

Humans have been selectively breeding cats and dogs for thousands of years to make more desirable pets. A new startup called the Los Angeles Project aims to speed up that process with genetic engineering to make glow-in-the-dark rabbits, hypoallergenic cats and dogs, and possibly, one day, actual unicorns.

The Los Angeles Project is the brainchild of biohacker Josie Zayner, who in 2017 publicly injected herself with the gene-editing tool Crispr during a conference in San Francisco and livestreamed it. "I want to help humans genetically modify themselves," she said at the time. She's also given herself a fecal transplant and a DIY Covid vaccine and is the founder and CEO of The Odin, a company that sells home genetic-engineering kits.

Now, Zayner wants to create the next generation of pets. "I think, as a human species, it's kind of our moral prerogative to level up animals," she says.

Cofounded with biotech entrepreneur Cathy Tie, a former Thiel Fellow, the Los Angeles Project is all about making animals that are "more complex and interesting and beautiful and unique" than ones that currently exist, Zayner says. The Austin-based company's name is a nod to another controversial effort—the Manhattan Project, which developed the first atomic bomb during WWII.

Photograph: Los Angeles Project

For the past year, the Los Angeles Project has been operating in stealth mode while its five-person team has been experimenting on embryos from frogs, fish, hamsters, and rabbits. They've used Crispr to delete genes and insert new ones—the latter being more technically difficult to achieve. They're also testing out a lesser-known technique known as restriction enzyme mediated integration, or REMI, for integrating new DNA into embryos. Making these modifications at the embryo level changes the genetic makeup of the resulting animal.

The team has used Crispr to add a gene to rabbit embryos so they produce green fluorescent protein, or GFP. Zayner says they're aiming to transfer the engineered embryos to female rabbits this week. If all goes well, the company will have glowing baby bunnies in a month. (Rabbits have a gestation period of just 31 to 33 days.)

They won't be the first glowing animals ever created. GFP is commonly used by scientists to visually track and monitor gene activity or cellular processes within an organism, often to study diseases. Researchers have previously made fluorescent rodents, monkeys, dogs, cats, and rabbits, but none of these animals were created for commercial purposes. But the Los Angeles Project is designing glowing bunnies and other animals to sell to consumers. "I think the pet space is huge and totally undervalued," Zayner says.

Fish genetically engineered to have the GFP protein are sold in pet stores across the country. Called GloFish, they were made with an older technique called recombinant DNA technology. The company that developed the fish, Yorktown Technologies, sold the brand for $50 million in 2017.

The Los Angeles Project is starting with the GFP edit because it's relatively simple. It's also observable in embryos when they're exposed to blue or ultraviolet light, showing that the gene editing worked. After fluorescent bunnies, the company has its sights on making cats that lack the Fel d1 protein, the primary allergen that cats produce, but also jackalopes, dragons, and unicorns. But more complex editing will be needed to achieve those more ambitious creations.

"As we continue, our goal is to really look at multiple genes at the same time, really understand the multiple genes that contribute towards a very complex trait, and then be able to transfer those changes from one species to another," Tie says. One company, eGenesis, has made pigs with 69 gene edits to make their organs more compatible for human transplants.

"I'm personally really interested in the unicorn," Tie says. It's a tall order that would require understanding the genetics behind the narwhal's twisted horn, then figuring out how to transfer it into a small animal first before engineering it into a horse. "Big ideas take a long time to achieve, and as a company, you have to evolve to meet the needs of the market but also really understand the long-term vision of the technology that you're building," she says.

Crispr is microinjected into embryos to modify an organism's genes.

Photograph: Los Angeles Project

The idea of making gene-edited pets is sure to raise eyebrows. In fact, bioethicists warned about such "frivolous" uses of CRISPR a decade ago when the technology was in its infancy. The company's glowing rabbits will be an initial test to see how consumers respond.

"I think most people are going to think it's crazy and will dismiss it as crazy," says Andy Weissman of Union Square Ventures, who has personally invested in the Los Angeles Project. "You're trying to convince people to come into a reality that doesn't yet exist."

He sees the company as part business, part art project. "We'll find out if they can accomplish both, or just one or the other."

There's the question of what happens if something goes wrong. Crispr can cause unintended edits, which could lead to cancer or other health problems in an animal. Plus, no one really knows how many edits can be made to an animal's genome without causing harm.

"We don't want to harm animals," Tie says. Both she and Zayner say they take the treatment of animals seriously. The company has not killed any animals for its experiments and doesn't plan to. They create the embryos by mixing eggs and sperm sourced from ovaries and testes they get from veterinarians and a local butcher.

And GloFish offer a cautionary tale. In Brazil, the fluorescent fish have escaped fish farms and are multiplying in creeks in the Atlantic Forest, raising concerns about whether they pose a threat to native species. Zayner says the animals they create would be spayed and neutered so they wouldn't be able to reproduce and pass on the genetic changes to offspring,

The company has been in touch with the US Food and Drug Administration about its plans, but it's unclear how the agency would regulate them. Back in 2003, the FDA determined that the sale of transgenic GloFish were not subject to regulation, based on evidence that the fish do not pose a risk to public health or the environment.

Zayner's new venture will no doubt test the bounds of gene-editing regulation, as her self-experimentation and DIY genetic engineering kits have in the past. But the Los Angeles Project may also spark much-needed societal conversations around what humans can—and should—do with genetic engineering.

"The crazy thing is, this technology is so advanced, and nobody's doing shit with it," Zayner says. "That's kind of our motto: Let's do stuff with it."

Intellia Therapeutics Announces Fourth Quarter And Full-Year 2024 Financial Results And Highlights Recent Company Progress

Dosed first patient in global Phase 3 HAELO study evaluating NTLA-2002 for hereditary angioedema (HAE)

Expect to complete enrollment of the HAELO study in the second half of 2025 and submit a Biologics License Application in the second half of 2026 to support plans for U.S. Launch in 2027

Enrollment in the pivotal Phase 3 MAGNITUDE trial of nexiguran ziclumeran (nex-z) in patients with transthyretin amyloidosis (ATTR) with cardiomyopathy continues to track ahead of projections; more than 550 total patients expected to be enrolled by year end

Actively screening for the Phase 3 MAGNITUDE-2 trial for nex-z in hereditary ATTR amyloidosis with polyneuropathy; on track to dose first patient in 1Q25

Ended 2024 with approximately $862 million in cash, cash equivalents and marketable securities

CAMBRIDGE, Mass., Feb. 27, 2025 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies, today reported operational highlights and financial results for the fourth quarter and year ended December 31, 2024.

"We are off to an excellent start in 2025 with renewed focus and strong operational execution across our three, pivotal Phase 3 studies," said Intellia President and Chief Executive Officer John Leonard, M.D. "We are excited by the clinical data presented during the fourth quarter. Our Phase 1/2 results in HAE suggest that NTLA-2002 could represent a functional cure for patients with HAE – for the first time a patient has the potential to be both free from attacks and free from chronic therapy. Similarly, the rapid, deep and durable reductions in serum TTR demonstrated to date in our Phase 1 study of nex-z in ATTR represent a highly differentiated profile that may offer patients an opportunity to stabilize or improve their clinical readouts in an otherwise unrelenting, progressive disease."

Fourth Quarter 2024 and Recent Operational Highlights

Hereditary Angioedema (HAE)

NTLA-2002: NTLA-2002 is a wholly owned, investigational in vivo CRISPR-based therapy designed to knock out the KLKB1 gene in the liver, with the goal of lifelong control of HAE attacks after a single dose.

In January, Intellia announced the first patient was dosed with NTLA-2002 in the global Phase 3 HAELO study. The Company expects to complete enrollment in the second half of 2025.

The Company plans to submit a Biologics License Application in the second half of 2026 to support plans for a U.S. Launch in 2027.

Intellia expects to present longer-term data from the ongoing Phase 1/2 study in 2025. The data will include patients in the Phase 2 portion who initially received a 25 mg dose or placebo and were subsequently given the 50 mg dose of NTLA-2002 selected for the Phase 3 study.

Transthyretin (ATTR) Amyloidosis

Nexiguran ziclumeran (nex-z, also known as NTLA-2001): Nex-z is an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene in liver cells, thereby preventing the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. Nex-z offers the possibility of halting and reversing the disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose. Nex-z has been generally well tolerated across all patients and at all dose levels tested. The most common treatment-related adverse event was an infusion reaction, which were mild or moderate; all patients were able to receive the intended dose of nex-z. Intellia leads development and commercialization of nex-z in collaboration with Regeneron. 

ATTR Amyloidosis with Cardiomyopathy (ATTR-CM):

Enrollment in the pivotal Phase 3 MAGNITUDE trial is progressing ahead of our target projections and we anticipate enrollment to exceed 550 total patients by year end.

Intellia presented data from the ongoing Phase 1 study at the 2024 American Heart Association (AHA) Scientific Sessions and published the findings online in the New England Journal of Medicine. Across all patients (n=36), a single dose of nex-z led to consistently rapid, deep and sustained serum TTR reduction, regardless of baseline levels, through the latest follow-up. At month 12, the mean serum TTR reduction was 90%, and the mean absolute residual serum TTR concentration was 17 µg/mL. With 11 patients who have reached 24 months of follow-up, all patients continued to show a sustained response with no evidence of a waning effect over time. The consistently low levels of serum TTR are anticipated to reduce the rate of ongoing amyloid formation and potentially allow for amyloid clearance and improvement in cardiac function. Nex-z was generally well tolerated across all patients.

Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN):

We are actively screening patients for the Phase 3 MAGNITUDE-2 study and are on track to dose the first patient in the first quarter of 2025.

Intellia presented data from the ongoing Phase 1 study in November. At month 12, patients who received a dose of 0.3 mg/kg or higher (n=33) had a mean serum TTR reduction of 91% and mean absolute residual serum TTR concentration of 20 µg/mL. For the 16 patients who reached 24 months of follow-up, there was no change to their post-dose TTR levels. It is anticipated that greater TTR reduction may lead to a greater clinical benefit in patients with ATTRv-PN. Nex-z was generally well tolerated across all patients and at all dose levels tested.

In November, Intellia announced the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) to nex-z for the treatment of ATTRv-PN.

Intellia expects to present longer-term data from both ATTR-CM and ATTRv-PN patients in the Phase 1 study in 2025. The data will include updated measures of clinical efficacy and safety.

Platform Update

Intellia continues to apply novel technologies, such as CRISPR-based gene editing technologies and lipid nanoparticle (LNP) delivery technologies, to develop in vivo and ex vivo product candidates. Treating—and potentially curing—a broad range of severe diseases requires the application of multiple technologies. With Intellia's proprietary technology at the core of the platform, the Company continues to research and develop new gene editing and delivery technologies to expand the therapeutic opportunities, furthering progress on the frontier of genetic medicine.

Corporate Update

On January 9, 2025, the Company announced that, after a strategic review of its business, it elected to prioritize late-stage programs – NTLA-2002 for HAE and nex-z for ATTR amyloidosis – and select research investments to focus on near-term value creation. As a result, the Company discontinued NTLA-3001 and other, undisclosed programs, and is reducing its workforce by approximately 27% in 2025. The Company expects to incur charges of approximately $8.0 million for severance and other employee termination-related costs in the first quarter of 2025.

Upcoming Events

The Company will participate in the following events during the first quarter of 2025:

AAAAI/WAO Joint Congress, March 1, San Diego

TD Cowen 45th Annual Health Care Conference, March 4, Boston

Leerink 2025 Global Biopharma Conference, March 10, Miami

Barclays 27th Annual Global Healthcare Conference, March 11, Miami

Jefferies Biotech on the Beach Summit, March 12, Miami

Fourth Quarter and Full-Year 2024 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $861.7 million as of December 31, 2024, compared to $1.0 billion as of December 31, 2023. The Company's cash position as of December 31, 2024, is expected to fund operations into the first half of 2027.

Collaboration Revenue: Collaboration revenue was $12.9 million during the fourth quarter of 2024, compared to negative $1.9 million during the fourth quarter of 2023. The $14.8 million increase was mainly driven by collaboration revenue received under the Regeneron agreements.   

R&D Expenses: Research and development (R&D) expenses were $116.9 million during the fourth quarter of 2024, compared to $109.0 million during the fourth quarter of 2023. The $7.9 million increase was primarily driven by the advancement of our lead programs. Stock-based compensation expense included in R&D expenses was $24.4 million for the fourth quarter of 2024.

G&A Expenses: General and administrative (G&A) expenses were $32.4 million during the fourth quarter of 2024, compared to $29.0 million during the fourth quarter of 2023. The $3.4 million increase was primarily related to stock-based compensation. Stock-based compensation expense included in G&A expenses was $15.2 million for the fourth quarter of 2024.

Net Loss: Net loss was $128.9 million for the fourth quarter of 2024, compared to $132.2 million during the fourth quarter of 2023.

Conference Call to Discuss Fourth Quarter and Full-Year 2024 Results

The Company will discuss these results on a conference call today, Thursday, February 27 at 8 a.M. ET.To join the call:

U.S. Callers should dial 1-833-316-0545 and international callers should dial 1-412-317-5726, approximately five minutes before the call. All participants should ask to be connected to the Intellia Therapeutics conference call.

Please visit this link for a simultaneous live webcast of the call.

A replay of the call will be available through the Events and Presentations page of the Investors & Media section on Intellia's website at intelliatx.Com, beginning on February 27 at 12 p.M. ET.

About Intellia TherapeuticsIntellia Therapeutics, Inc. (NASDAQ:NTLA) is a leading clinical-stage gene editing company focused on revolutionizing medicine with CRISPR-based therapies. Since its inception, Intellia has focused on leveraging gene editing technology to develop novel, first-in-class medicines that address important unmet medical needs and advance the treatment paradigm for patients. 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.

Forward-Looking StatementsThis press release contains "forward-looking statements" of Intellia Therapeutics, Inc. ("Intellia" or the "Company") within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia's beliefs and expectations concerning: the safety, efficacy, success and advancement of its clinical programs for NTLA-2001, also known as nexiguran ziclumeran or "nex-z", for transthyretin ("ATTR") amyloidosis and NTLA-2002 for the treatment of hereditary angioedema ("HAE") pursuant to its clinical trial applications ("CTA") and investigational new drug ("IND") submissions, including the expected timing of data releases, regulatory feedback, regulatory filings, and the initiation, enrollment, dosing and completion of clinical trials, such as the completion of enrollment of the Phase 3 HAELO study in the second half of 2025 and the submission of a biologics license application in the second half of 2026, its ability to rapidly enroll the Phase 3 MAGNITUDE study, the planned initiation of the Phase 3 trial MAGNITUDE-2 by year-end, the plan to dose the first patient in the global pivotal Phase 3 MAGNITUDE-2 trial in the first quarter of 2025, the potential of NTLA-2001 to halt and reverse disease by driving a deep, consistent and potentially lifelong reduction in TTR protein after a single dose, and the potential of NTLA-2002 to be a functional cure for patients with HAE and to demonstrate lifelong control of HAE attacks and chronic therapy after a single dose; its ability to apply novel technologies, such as CRISPR-based gene editing technologies and lipid nanoparticle (LNP) delivery technologies, to develop in vivo and ex vivo product candidates, including its ability to use those technologies to expand therapeutic opportunities and the timing expectations of advancing such product candidates; its ability to optimize the impact of its collaborations on its development programs, including, but not limited to, its collaboration with Regeneron Pharmaceuticals, Inc. ("Regeneron") and their co-development programs for ATTR amyloidosis; and its growth as a company and expectations regarding its uses of capital, expenses, future accumulated deficit and financial results, including its ability to fund operations into the first half of 2027.

Any forward-looking statements in this press release are based on management's current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia's ability to protect and maintain its intellectual property position; risks related to Intellia's relationship with third parties, including its contract manufacturers, collaborators, licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation and conduct of preclinical and clinical studies and other development requirements for its product candidates, including uncertainties related to regulatory approvals to conduct clinical trials; risks related to the ability to develop and commercialize any one or more of Intellia's product candidates successfully; risks related to the results of preclinical studies or clinical studies not being predictive of future results in connection with future studies; the risk that clinical study results will not be positive; risks related to the potential delay of planned clinical trials due to regulatory feedback or other developments; and risks related to Intellia's collaborations with Regeneron, or its other collaborations not continuing or not being successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in Intellia's most recent annual report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in Intellia's other filings with the Securities and Exchange Commission, including its quarterly report on Form 10-Q. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.

                              INTELLIA THERAPEUTICS, INC.     CONSOLIDATED STATEMENTS OF OPERATIONS (UNAUDITED)     (Amounts in thousands, except per share data)               Three Months Ended December 31,   Twelve Months Ended December 31,                 2024       2023       2024       2023       Collaboration revenue   $ 12,874     $ (1,917 )   $ 57,877     $ 36,275       Operating expenses:                       Research and development   116,877       108,981       466,311       435,069         General and administrative   32,444       28,994       125,829       116,497           Total operating expenses   149,321       137,975       592,140       551,566       Operating loss       (136,447 )     (139,892 )     (534,263 )     (515,291 )     Other income (expense), net:                             Interest income     10,631       12,459       47,807       49,832                 Change in fair value of investments, net   (3,082 )     -       (32,565 )     -                 Loss from equity method investment   -       (4,728 )     -       (15,633 )               Change in fair value of contingent consideration   -       -       -       (100 )         Total other income (expense), net   7,549       7,731       15,242       34,099       Net loss       $ (128,898 )   $ (132,161 )   $ (519,021 )   $ (481,192 )     Net loss per share, basic and diluted $ (1.27 )   $ (1.46 )   $ (5.25 )   $ (5.42 )     Weighted average shares outstanding, basic and diluted   101,855       90,461       98,849       88,770                                                     INTELLIA THERAPEUTICS, INC.   CONSOLIDATED BALANCE SHEET DATA (UNAUDITED)   (Amounts in thousands)                                   December 31, 2024   December 31, 2023   Cash, cash equivalents and marketable securities           $ 861,730   $ 1,012,087   Total assets           1,191,015     1,300,977   Total liabilities           319,059     250,808   Total stockholders' equity       871,956     1,050,169                      

Intellia Contacts:

Investors:Brittany ChavesSenior Manager, Investor Relationsbrittany.Chaves@intelliatx.Com

Media:Matt CrensonTen Bridge Communicationsmedia@intelliatx.Com  mcrenson@tenbridgecommunications.Com

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