Hemophilia B

DUBLIN--( BUSINESS WIRE )--The "Hemophilia B - Pipeline Insight, 2024" report has been added to ResearchAndMarkets.com's offering. Significant advances in the treatment and management of Hemophilia B are forthcoming, according to a new comprehensive research publication now available on our website. This insightful report unveils a robust and diverse therapeutic pipeline, promising enhancements in care for individuals living with this rare genetic disorder. The culmination of data provides in-depth knowledge regarding over 15 companies' endeavors and over 20 pipeline drugs spanning clinical and nonclinical development stages. Global Research Gains on Hemophilia B Therapeutics The global coverage within this report transcends geographical boundaries, providing a universal perspective on the research and development efforts aimed at combatting Hemophilia B. This disorder, stemming from a deficiency of factor IX clotting activity, often leads to bleeding episodes that can be life-altering for those afflicted. The report details each therapy’s development phase, including Phase III and late-stage products, thereby offering stakeholders a clarion view into potential forthcoming treatments. Insights into Diagnostic Processes and Treatment Regimens The report elucidates the complexity of Hemophilia B diagnosis and underscores the importance of comprehensive blood coagulation tests. Furthermore, it delves into the nuances of replacement therapy - the current cornerstone of Hemophilia B management. Prophylaxis and other advanced treatment strategies are also discussed, highlighting gene therapy as an emerging powerhouse in the realm of Hemophilia B therapeutic options. Emerging Drugs and Key Players in Hemophilia B Therapeutics BBM-H901 by Belief Biomed is currently in the limelight as it strides into Phase III trials, presenting itself as a potential gene therapy candidate. TU7710, developed by TiumBio, offers a novel approach for patients with neutralizing antibodies and is currently under Phase I investigation. Innovative Strategies for Hemophilia B Treatment Within this comprehensive report, readers will uncover the extensive range of drugs in various development stages, from preclinical discovery to Phase III trials, emphasizing the industry's dynamic approach towards eradicating the challenges associated with Hemophilia B. The document scrutinizes multiple drug profiles, bringing forth their mechanistic actions, and shines a light on critical therapeutic assessments. Discoveries Set to Transform Hemophilia B Clinical Landscape The publication underscores the unmet needs within Hemophilia B therapeutic research and how the current pipeline is poised to address these gaps. The extensive catalog of developmental activities, including collaborations, mergers, and acquisitions, suggests a sector ripe with innovation and dedication to improving patient outcomes. A selection of companies mentioned in this report includes Shanghai Vitalgen BioPharma Belief BioMed TiumBio Jiangsu Gensciences Centessa Pharmaceuticals Pfizer OPKO Health Bayer Takeda Sanofi For more information about this report visit https://www.researchandmarkets.com/r/gfbg6e About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

~ Presented promising clinical update from U.S. and European Phase I/II trials of AMT-130 in Huntington’s disease; Up to three years of follow-up data to be presented in mid-2024; Regulatory interactions and clarity on potential strategies for clinical development expected in 2024 ~ ~ Announced FDA clearance of two Investigational New Drug (IND) applications; Initiation of Phase I/II clinical trials in mesial temporal lobe epilepsy (mTLE) and Fabry disease, in addition to SOD1-ALS, are expected in the first half of 2024 ~ ~ Announced strategic reorganization to advance multiple clinical-stage programs and deliver $180 million of cost savings over the next three years ~ ~ Cash position of approximately $618 million as of December 31, 2023 expected to fund operations into the second quarter of 2027 ~ LEXINGTON, Mass. and AMSTERDAM, Feb. 28, 2024 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today reported its financial results for the fourth quarter and full year 2023 and highlighted recent progress across its business. “We are pleased with the progress made across the company in 2023 and are now laser-focused on execution across multiple clinical programs,” stated Matt Kapusta, chief executive officer of uniQure. “Our top priorities are to engage with regulatory authorities to clarify the approval pathway for AMT-130 in Huntington’s disease and to initiate patient enrollment across three additional clinical trials as expeditiously as possible.” “While we enter 2024 with a strong balance sheet, we remain disciplined on the prudent and efficient allocation of our capital,” he continued. “Any decision to advance AMT-130 into late-stage development will necessitate a clear and timely approval pathway and financial feasibility, including through a partnership which we would secure before beginning any Phase III trial.” Recent Updates Advancing AMT-130 for the treatment of Huntington’s disease In December 2023, the Company announced updated clinical data from the ongoing U.S. and European Phase I/II studies of AMT-130 for the treatment of early-stage Huntington’s disease. Patients treated with AMT-130 continued to show evidence of preserved neurological function with potential dose-dependent clinical benefits relative to a non-concurrent criteria-matched natural history of the disease. When compared to the expected rate of decline from an inclusion criteria-matched natural history data set, AMT-130 showed favorable trends in composite Unified Huntington’s Disease Rating Scale (cUHDRS), Total Functional Capacity (TFC) and Total Motor Score (TMS) key clinical rating scales designed to assess disease progression. Further declines in neurofilament light chain (NfL), an exploratory biomarker for the measurement of neuronal degradation and disease progression were observed among patients treated with AMT-130. Mean NfL in the cerebrospinal fluid (CSL) for low-dose patients remained below baseline at 30 months of follow-up and high-dose patients were near baseline at 18 months. AMT-130 continued to be generally well-tolerated with a manageable safety profile across both doses. In the fourth quarter of 2023, the Company initiated patient dosing in a third cohort of up to 12 patients to further investigate both doses of AMT-130 in combination with perioperative immunosuppression, with a focus on evaluating near-term safety and tolerability. Enrollment in this cohort is expected to be completed in the second half of 2024. In the second quarter of 2024, the Company expects to initiate regulatory interactions with the U.S. Food and Drug Administration (FDA) to discuss data from the ongoing Phase I/II studies and potential strategies for the further development of AMT-130. By the end of 2024, the Company expects to have greater clarity regarding a potential approval pathway for AMT-130.In mid-2024, the Company expects to provide an interim update from the ongoing Phase I/II studies of AMT-130, including up to 24- and 36-month follow-up data from all treated patients in the U.S. and European trials. Advancing additional programs into the clinic AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (rMTLE) – In September 2023, the Company announced the clearance of an IND for the Phase I/IIa clinical study of AMT-260. Site initiation is underway, and patient enrollment is expected to begin in the first half of 2024.AMT-162 for the treatment of SOD1 amyotrophic lateral sclerosis (ALS) - In January 2023, the Company entered into a global licensing agreement with Apic Bio for ABP-102, now known as AMT-162, for the treatment of superoxide dismutase 1 (SOD1) ALS, a rare, genetic form of ALS. Patient enrollment in a Phase I/II clinical trial is expected to begin in the first half of 2024.AMT-191 for the treatment of Fabry disease – In November 2023, the Company announced the clearance of an IND for the Phase I/IIa clinical study of AMT-191. Patient enrollment is expected to begin in the first half of 2024. Generating value from the commercial launch of HEMGENIX® The Company continues to provide commercial supply of etranacogene dezaparvovec (HEMGENIX®) to its partner CSL Behring and manufactures the product at its cGMP facility in Lexington, MA. The Company is one of a select number of gene therapy companies with a qualified facility producing routine commercial manufacturing for the market. Upcoming Investor Events 44th Annual Cowen Health Care Conference, March 5, 2024 – Boston, MALeerink Global Biopharma Conference 2024, March 12, 2024 – Miami, FLUBS Virtual CNS Day, March 18, 2024 Financial Highlights Cash position: As of December 31, 2023, the Company held cash and cash equivalents and investment securities of $617.9 million, compared to $392.8 million as of December 31, 2022. The Company entered into a royalty agreement in May 2023 and received an upfront payment of $375.0 million, and collected $100.0 million in July 2023 for a milestone due from CSL following the first sale of HEMGENIX® in the U.S. The Company expects cash, cash equivalents and investment securities will fund operations into the second quarter of 2027. Revenues: Revenue for the year ended December 31, 2023 was $15.8 million, compared to $106.5 million in the same period in 2022. Revenues in 2022 included $100.0 million of license revenue related to the U.S. first sale milestone payment of HEMGENIX® that the Company expected to receive in 2023. Revenue from contract manufacturing HEMGENIX® for CSL increased $9.1 million in 2023 compared to 2022. Cost of contract manufacturing revenues: Cost of contract manufacturing revenues were $13.6 million for the year ended December 31, 2023, compared to $2.1 million for the same period in 2022. The increase relates to an increase in activities related to contract manufacturing HEMGENIX® for CSL. R&D expenses: Research and development expenses were $214.9 million for the year ended December 31, 2023, compared to $197.6 million during the same period in 2022. The $17.2 million increase was primarily related to a $5.9 million net increase of external research and development expenses including a $10.0 million payment made to Apic Bio to acquire AMT-162, an $8.8 million non-cash increase related to the fair value of contingent consideration associated with the Company’s acquisition of Corlieve Therapeutics in 2021 as well as a $1.4 million non-cash impairment loss related to our Lexington research facility. SG&A expenses: Selling, general and administrative expenses were $74.6 million for the year ended December 31, 2023, compared to $55.1 million during the same period in 2022. The $19.5 million increase was primarily related to a $9.7 million increase of professional, financial advisory and intellectual property fees, a $3.7 million increase in information technology expenses as well as a $3.7 million increase in personnel and contractor-related expenses. Other non-operating items, net: Other non-operating items, net was an expense of $23.7 million for the year ended December 31, 2023, compared to net income of $14.9 million for the same period in 2022. The $38.6 million decrease in other non-operating items, net was primarily related to a decrease in foreign currency gains, net of $24.9 million and an increase in non-cash interest expense of $26.9 million related to the royalty agreement that the Company entered into in May 2023, which partially was offset by an increase of $19.0 million in interest income earned on investment securities and cash on hand. Net loss:The net loss for the year ended December 31, 2023, was $308.5 million, or $6.47 basic and diluted loss per ordinary share, compared to $126.8 million net loss for the same period in 2022, or $2.71 basic and diluted loss per ordinary share. About uniQure uniQure’s mission is to reimagine the future of medicine by delivering innovative cures that transform lives. The recent approvals of our gene therapy for hemophilia B – a historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. We are now leveraging our modular and validated technology and manufacturing platform to advance a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (ALS), Fabry disease, and other severe diseases. www.uniQure.com uniQure Forward-Looking Statements This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," “establish,” "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," “seek,” "should," "will," "would" and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Examples of these forward-looking statements include, but are not limited to, statements concerning the Company’s cash runway and its ability to fund its operations into the second quarter of 2027; the Company’s expected cost savings related to its strategic reorganization; the Company’s plans to announce additional follow up data from the ongoing U.S. and European Phase I/II clinical studies of AMT-130; the Company’s plans to initiate interactions with regulatory authorities regarding the further development of AMT-130 and the timing of regulatory clarity from such interactions; and the Company’s plans to initiate patient enrollment for AMT-260, AMT-162 and AMT-191 in the first half of 2024. The Company’s actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, among others: risks associated with the clinical results and the development and timing of the Company’s programs; the Company’s interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials and pathways to approval; the Company’s ability to continue to build and maintain the company infrastructure and personnel needed to achieve its goals; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the Company’s ability to obtain, maintain and protect intellectual property; the Company’s ability to fund its operations and to raise additional capital as needed; and the impact of global economic uncertainty, rising inflation, rising interest rates or market disruptions on its business. These risks and uncertainties are more fully described under the heading "Risk Factors" in the Company’s periodic filings with the U.S. Securities & Exchange Commission (“SEC”), including its Annual Report on Form 10-K filed February 28, 2024 and in other filings that the Company makes with the SEC from time to time. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future. uniQure Contacts: FOR INVESTORS: FOR MEDIA: Maria E. CantorChiara RussoTom MaloneDirect: 339-970-7536Direct: 617-306-9137Direct: 339-970-7558Mobile: 617-680-9452Mobile: 617-306-9137Mobile: 339-223-8541m.cantor@uniQure.comc.russo@uniQure.comt.malone@uniQure.com uniQure N.V.UNAUDITED CONSOLIDATED BALANCE SHEETS December 31, December 31, 2023 2022 (in thousands, except share and per share amounts) Current assets Cash and cash equivalents$241,360 $228,012 Current investment securities 376,532 124,831 Accounts receivable and contract asset 4,193 102,376 Inventories, net 12,024 6,924 Prepaid expenses 15,089 11,817 Other current assets and receivables 2,655 2,814 Total current assets 651,853 476,774 Non-current assets Property, plant and equipment, net 46,548 50,532 Non-current investment securities — 39,984 Operating lease right-of-use assets 28,789 32,726 Intangible assets, net 60,481 58,778 Goodwill 26,379 25,581 Deferred tax assets, net 12,276 14,528 Other non-current assets 5,363 6,061 Total non-current assets 179,836 228,190 Total assets$ 831,689 $ 704,964 Current liabilities Accounts payable$6,586 $10,984 Accrued expenses and other current liabilities$30,534 $30,571 Current portion of contingent consideration 28,211 25,982 Current portion of operating lease liabilities 8,344 8,382 Total current liabilities 73,675 75,919 Non-current liabilities Long-term debt 101,749 102,791 Liability from royalty financing agreement 394,241 — Operating lease liabilities, net of current portion 28,316 31,719 Contingent consideration, net of current portion 14,795 9,334 Deferred tax liability, net 7,543 8,257 Other non-current liabilities 3,700 935 Total non-current liabilities 550,344 153,036 Total liabilities 624,019 228,955 Shareholders' equity Total shareholders' equity 207,670 476,009 Total liabilities and shareholders' equity$ 831,689 $ 704,964 Balancing check - - uniQure N.V.UNAUDITED CONSOLIDATED STATEMENTS OF OPERATIONS Years ended December 31, 2023 2022 2021 (in thousands, except share and per share amounts)License revenues$2,758 $100,000 $517,400 Contract manufacturing revenues 10,835 1,717 - Collaboration revenues 2,250 4,766 6,602 Total revenues 15,843 106,483 524,002 Operating expenses: Cost of license revenues (65) (1,254) (24,976)Cost of contract manufacturing revenues (13,563) (2,089) - Research and development expenses (214,864) (197,591) (143,548)Selling, general and administrative expenses (74,591) (55,059) (56,290)Total operating expenses (303,083) (255,993) (224,814)Other income 6,059 7,171 12,306 Other expense (1,690) (820) (876)(Loss) / income from operations (282,871) (143,159) 310,618 Non-operating items, net (23,686) 14,900 22,188 (Loss) / income before income tax (expense) / benefit$ (306,557) $ (128,259) $ 332,806 Income tax (expense) / benefit (1,921) 1,470 (3,217)Net (loss) / income$ (308,478) $ (126,789) $ 329,589 Earnings per ordinary share - basic Basic net (loss) / income per ordinary share$(6.47) $(2.71) $7.17 Earnings per ordinary share - diluted Diluted net (loss) / income per ordinary share$(6.47) $(2.71) $7.04 Weighted average shares - basic 47,670,986 46,735,045 45,986,467 Weighted average shares - diluted 47,670,986 46,735,045 46,840,972

On track to dose the first patient in the Phase 3 MAGNITUDE trial of NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis with cardiomyopathy in Q1 2024Expect to initiate the Phase 3 study of NTLA-2002 for the treatment of hereditary angioedema (HAE) in 2H24Plan to present new clinical data in 2024 from both ongoing NTLA-2001 and NTLA-2002 first-in-human studies, including NTLA-2002 Phase 2 results Published positive interim results from the Phase 1 study of NTLA-2002 in the New England Journal of MedicineOn track to dose the first patient in the Phase 1 study of NTLA-3001, an in vivo gene insertion candidate for the treatment of alpha-1 antitrypsin deficiency (AATD)-associated lung disease, in 2024Expanding development of in vivo CRISPR-based therapies to target tissues outside of the liver; announced strategic collaboration with ReCode to develop novel gene editing therapies for cystic fibrosis Ended 2023 in a strong financial position with approximately $1.0 billion in cash CAMBRIDGE, Mass., Feb. 22, 2024 (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, 2023. “We’re off to a very strong start in 2024 as we execute against our strategic priorities to realize the full potential of CRISPR-based gene editing,” said Intellia President and Chief Executive Officer John Leonard, M.D. “We are focused on rapidly enrolling patients in the pivotal Phase 3 MAGNITUDE trial of NTLA-2001 for the treatment of ATTR amyloidosis with cardiomyopathy and expect to dose the first patient in the first quarter of this year. We also remain on track to begin the Phase 3 trial for our second in vivo CRISPR-based therapy, NTLA-2002 for hereditary angioedema, later in the year. At the same time, we continue to expand both the technical approaches for CRISPR-based therapies, as well as the range of diseases they can potentially address. We plan to initiate two first-in-human studies for product candidates leveraging our modular gene insertion platform to produce a deficient protein – one wholly owned program focused on alpha-1 antitrypsin deficiency-associated lung disease and, together with Regeneron, a second program focused on hemophilia B. Finally, we are progressing our editing capabilities, including DNA writing, and applying them to diseases that originate outside of the liver. We announced last week a new collaboration with ReCode Therapeutics to advance novel gene editing treatments directly to the lung in patients with cystic fibrosis. These pipeline and platform efforts move us closer to setting a new standard of care for people living with serious diseases and expanding Intellia’s impact as the leading gene editing company.” Fourth Quarter 2023 and Recent Operational Highlights Transthyretin (ATTR) Amyloidosis NTLA-2001: NTLA-2001 is an investigational in vivo CRISPR-based therapy designed to inactivate the TTR gene in the liver and thereby prevent the production of transthyretin (TTR) protein for the treatment of ATTR amyloidosis. NTLA-2001 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. Intellia leads development and commercialization of NTLA-2001 in collaboration with Regeneron. ATTR Amyloidosis with Cardiomyopathy (ATTR-CM): Intellia is actively enrolling patients, including in the U.S., in the pivotal Phase 3 MAGNITUDE trial. The Company is on track to dose the first patient in Q1 2024 and continues to open new clinical sites. Hereditary ATTR Amyloidosis with Polyneuropathy (ATTRv-PN): Intellia is actively preparing for a global pivotal Phase 3 study of NTLA-2001 for the treatment of ATTRv-PN. The Company plans to present updated data from the ongoing Phase 1 study in 2024. 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. Intellia plans to initiate the global pivotal Phase 3 study, including U.S. patients, in the second half of 2024, subject to regulatory feedback.As previously announced in January, Intellia completed enrollment and dosing in the Phase 2 portion of the Phase 1/2 study in adults with HAE. The Company plans to present updated data from the Phase 1 and new data from the Phase 2 portion in 2024.In January, the Company announced that positive interim results from the Phase 1 portion of the Phase 1/2 study of NTLA-2002 were published in the New England Journal of Medicine (NEJM). The reported data showed that a single dose of NTLA-2002 led to a 95% mean reduction in monthly HAE attack rate across all 10 patients in the Phase 1 portion. NTLA-2002 was well tolerated at all dose levels. The most frequent adverse events reported were mild, transient infusion-related reactions and fatigue.During the fourth quarter of 2023, Intellia received Priority Medicines (PRIME) designation from the European Medicines Agency and orphan drug designation from the European Commission for NTLA-2002. In Vivo Targeted Gene Insertion NTLA-3001 for Alpha-1 Antitrypsin Deficiency (AATD)-Associated Lung Disease: NTLA-3001 is a wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the alpha-1 antitrypsin (A1AT) protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. In December 2023, Intellia submitted a Clinical Trial Application (CTA) to initiate a first-in-human, Phase 1 study of NTLA-3001. The Company plans to dose the first patient in 2024. Hemophilia B: In February, Regeneron and Intellia announced the clearance by the U.S. Food and Drug Administration of its investigational new drug application to initiate a clinical trial of its investigational in vivo CRISPR-based Factor 9 gene insertion program for people living with hemophilia B. A Phase 1, first-in-human study is expected to begin in mid-2024. Regeneron leads development and commercialization of hemophilia A and B programs in collaboration with Intellia. In Vivo Platform Expansion Including to Tissues Outside of the Liver In February, Intellia and ReCode announced a strategic collaboration to develop novel genomic medicines for the treatment of cystic fibrosis (CF). The collaboration will leverage Intellia’s proprietary CRISPR-based gene editing platform, including its DNA writing technology, and ReCode’s proprietary Selective Organ Targeting (SORT) lipid nanoparticle delivery platform to precisely correct one or more CF disease-causing gene mutations. In October 2023, Intellia and Regeneron announced an expanded research collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases.In October 2023, Regeneron exercised its option to extend the existing technology collaboration term with Intellia for two years. The technology collaboration term now extends to April 2026, and Intellia will receive a $30 million payment due in April 2024. Ex Vivo Program Updates Intellia is advancing multiple preclinical programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The Company’s proprietary allogeneic cell engineering platform is designed to avoid both T cell- and NK cell-mediated rejection, a key unsolved challenge with other investigational allogeneic approaches. Upcoming Events The Company will participate in the following events in March: TD Cowen 44th Annual Health Care Conference, March 4, BostonLeerink Global Biopharma Conference, March 12, MiamiBarclays Global Healthcare Conference, March 13, Miami Fourth Quarter and Full-Year 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $1.0 billion as of December 31, 2023, compared to $1.3 billion as of December 31, 2022. The decrease was driven by cash used to fund operations of $448.8 million. The decrease was offset in part by $119.8 million of net equity proceeds from the Company’s “At the Market” (ATM) program, $49.8 million of interest income, $18.7 million of reimbursement from its collaborators, and $10.5 million in proceeds from employee-based stock plans. The cash position is expected to fund operations into mid-2026.Collaboration Revenue: Collaboration revenue decreased by $15.5 million to negative $1.9 million during the fourth quarter of 2023, compared to $13.6 million during the fourth quarter of 2022. This decrease was mainly driven by a $10.3 million one-time revenue recognition adjustment related to Regeneron extending the technology collaboration to April 2026. Intellia will receive a $30.0 million payment due in April 2024 as part of the Regeneron extension.R&D Expenses: Research and development expenses increased by $9.0 million to $109.0 million during the fourth quarter of 2023, compared to $100.0 million during the fourth quarter of 2022. This increase was primarily driven by the advancement of our lead programs and personnel growth to support these programs. Stock-based compensation expense included in research and development expenses was $21.7 million for the fourth quarter of 2023.G&A Expenses: General and administrative expenses increased by $5.4 million to $29.0 million during the fourth quarter of 2023, compared to $23.6 million during the fourth quarter of 2022. This increase was primarily related to an increase in stock-based compensation of $4.3 million. Stock-based compensation expense included in general and administrative expenses was $13.3 million for the fourth quarter of 2023.Net Loss: The Company’s net loss was $132.2 million for the fourth quarter of 2023, compared to $113.4 million during the fourth quarter of 2022. Conference Call to Discuss Fourth Quarter and Full-Year 2023 Results The Company will discuss these results on a conference call today, Thursday, February 22, 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 22, 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. 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. Forward-Looking Statements This 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 for transthyretin (“ATTR”) amyloidosis, NTLA-2002 for the treatment of hereditary angioedema (“HAE”), and NTLA-3001 for the treatment of alpha-1 antitrypsin deficiency (“AATD”)-associated lung disease, 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 presentation of additional data from the NTLA-2001 and NTLA-2002 clinical trials in 2024, dosing of the first patient in its global pivotal Phase 3 MAGNITUDE trial for NTLA-2001 in Q1 2024 and its ability to rapidly enroll this study, the planned initiation of a global pivotal Phase 3 study of NTLA-2002 in 2H 2024 subject to regulatory feedback, its ability to dose the first patient in its NTLA-3001 Phase 1 study in 2024, and the potential of NTLA-3001 to restore permanent expression of functional alpha-1 antitrypsin protein to therapeutic levels after a single dose; the expansion of its CRISPR/Cas9 technology and related novel technologies, including DNA writing and related research milestones and delivery to other tissues outside of the liver; its ability to advance multiple ex vivo programs utilizing an allogeneic platform, which is designed to avoid both T cell- and NK cell-mediated rejection, for the treatment of immuno-oncology and autoimmune diseases; its ability to advance additional in vivo and ex vivo development candidates and timing expectations of advancing such development candidates and releasing data related to such technologies and development 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 Hemophilia B, as well as their expanded research collaboration to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases and its collaboration with ReCode Therapeutics, Inc. (“ReCode”) to develop novel genomic medicines for the treatment of cystic fibrosis utilizing CRISPR-based gene editing, including DNA writing, and Selective Organ Targeting lipid nanoparticle delivery technologies; and its growth as a Company and expectations regarding its uses of capital, expenses, future accumulated deficit and financial results. 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, 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, ReCode, 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. 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, 2023 2022 2023 2022 Collaboration revenue $(1,917) $13,573 $36,275 $52,121 Operating expenses: Research and development 108,981 100,034 435,069 419,979 General and administrative 28,994 23,626 116,497 90,306 Total operating expenses 137,975 123,660 551,566 510,285 Operating loss (139,892) (110,087) (515,291) (458,164) Other income (expense), net: Interest income 12,459 5,354 49,832 8,542 Loss from equity method investment (4,728) (3,248) (15,633) (11,079) Change in fair value of contingent consideration - (5,426) (100) (13,485) Total other income (expense), net 7,731 (3,320) 34,099 (16,022) Net loss $(132,161) $(113,407) $(481,192) $(474,186) Net loss per share, basic and diluted$(1.46) $(1.40) $(5.42) $(6.16) Weighted average shares outstanding, basic and diluted 90,461 81,223 88,770 76,972 INTELLIA THERAPEUTICS, INC. CONSOLIDATED BALANCE SHEET DATA (UNAUDITED) (Amounts in thousands) December 31,2023 December 31,2022 Cash, cash equivalents and marketable securities $1,012,087 $1,261,960 Total assets 1,300,977 1,520,114 Total liabilities 250,808 284,530 Total stockholders' equity 1,050,169 1,235,584 Intellia Contacts: Investors:Ian KarpSenior Vice President, Investor Relations and Corporate Communicationsian.karp@intelliatx.com Lina LiSenior Director, Investor Relations and Corporate Communicationslina.li@intelliatx.com Media:Matt CrensonTen Bridge Communicationsmedia@intelliatx.com mcrenson@tenbridgecommunications.com