PNPLA3

The phase II study led by Dr. Kenneth Cusi evaluating lanifibranor in patients with T2D and MASLD was selected as late breaker.Two additional scientific abstracts from the NATIVE Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH have been selected for presentation. The two abstracts show: the correlation between the increase of adiponectin under lanifibranor and the improvement of histological and serum markers of NASH severity both in terms of activity and fibrosis.the improvement of liver histology and markers of cardiometabolic health in patients with NASH treated with lanifibranor, independent of PNPLA3 genotype. Daix (France), Long Island City (New York, United States), November 6, 2023 – Inventiva (Euronext Paris and Nasdaq: IVA) (the “Company”), a clinical-stage biopharmaceutical company focused on the development of oral small molecule therapies for the treatment of nonalcoholic steatohepatitis (NASH) and other diseases with significant unmet medical needs, today announced that the phase II trial led by Dr. Cusi in patients with type two diabetes (T2D) has been accepted as late breaker, at the upcoming The Liver Meeting® 2023 hosted by the American Association for the Study of Liver Diseases on November 10-14, 2023 in Boston. In addition two other scientific abstracts have been selected for poster presentation. The late breaker abstract “Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)” presents results from a study sponsored by Dr. Cusi at the University of Florida, that evaluates the effect of lanifibranor on insulin resistance in the liver, muscle and adipose tissue, as well as its effect on intrahepatic triglyceride (IHTG) content in patients with T2D and Metabolic dysfunction associated steatotic liver disease (MASLD)1. The second abstract evaluates the correlation between adiponectin response with lanifibranor and the improvement of histological and serum markers of NASH severity, both in terms of disease activity and fibrosis. The change in adiponectin levels at end of treatment (categorized as unchanged, moderate or high increase) correlated positively to histological endpoints of NASH resolution and no worsening of fibrosis, improvement of fibrosis and no worsening of NASH, and NASH resolution and fibrosis improvement. The degree of adiponectin level increase correlated also with improvement of the NASH-CRN and SAF-Activity scores as well as with improvement of the individual components: steatosis, inflammation and ballooning. Lanifibranor-associated adiponectin increase also correlated with the improvement in histological fibrosis stage, pro-C3 levels and MACK-3 score. These data further support that adiponectin is a biomarker for the efficacy of lanifibranor treatment across the disease spectrum of NASH, from cardiometabolic health – as previously shown – to hepatic health. As a reminder, a 3.82 and 4.50 fold increase in adiponectin level were respectively reported in the 800mg arm and 1200mg arm during Inventiva’s NATIVE Phase IIb clinical trial. The third abstract evaluates the impact of the PNPLA3 variant I148M, which is strongly associated with risk for and the progression of NASH, on the histological and cardiometabolic response to lanifibranor. In a retrospective analysis of Inventiva’s NATIVE Phase IIb clinical trial evaluating lanifibranor for the treatment of patients with NASH, histological and circulating marker responses were evaluated by PNPLA3 genotype subgroup. The response to lanifibranor treatment on the histological endpoints was similar across the three PNPLA3 genotype (II/IM/MM) despite a higher activity score measured at baseline in patients with MM genotype.In addition, the improvement of cardiometabolic health markers (glycemic control, insulin, HOMA-IR, HsCRP, CAP and adiponectin) following treatment with lanifibranor was similar in the three PNPLA3 genotypes. These results demonstrate that the efficacy of lanifibranor on both liver histology and markers of cardiometabolic health appears to be independent of PNPLA3 status. The details of the presentation are as follows: Abstracts: Abstract title: “Lanifibranor reverses insulin resistance and improves glucose and lipid metabolism in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD)” Poster number: 5035-C Presentation type: Late breaker poster presentation Authors: Diana Barb, Srilaxmi Kalavalapalli, Eddison Godinez Leiva, Fernando Bril, Philippe Huot-Marchand, Lucile Dzen, Jean-Louis Junien, Pierre Broqua, Andrea Ortiz Rocha, Romina Lomonaco, Michael P Cooreman, Ken Cusi Date: November 12, 2023 – 1:00pm - 2:00pm (EST) Abstract title: “Lanifibranor-associated adiponectin increase correlates with improvement of histological and serum markers of NASH severity both in terms of activity and fibrosis” Poster number: 2458-C Presentation type: Poster presentation Authors: Michael P. Cooreman, Manal F. Abdelmalek, Philippe Huot-Marchand, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Sven Francque Date: November 11, 2023 – 8:30am - 5:00pm (EST) Abstract title: “Lanifibranor improves liver histology and markers of cardiometabolic health in patients with NASH independent of PNPLA3 genotype: a retrospective analysis of the native study” Poster number: 2457-C Presentation type: Poster presentation Authors: Louis Griffel, Sven Francque, Manal F. Abdelmalek, Philippe Huot-Marchand, Lucile Dzen, Martine Baudin, Jean-Louis Junien, Pierre Broqua, Michael P. Cooreman Date: November 11, 2023 – 8:30am - 5:00pm (EST) Inventiva will also be present with a booth: we are inviting you to visit us from Saturday November 11 through Monday November 13, 2023, during exhibition hall opening hours at booth #D3027 located in the exhibition hall of the conference center. About lanifibranor Lanifibranor, Inventiva’s lead product candidate, is an orally-available small molecule that acts to induce anti-fibrotic, anti-inflammatory and beneficial vascular and metabolic changes in the body by activating all three peroxisome proliferator-activated receptor (PPAR) isoforms, which are well-characterized nuclear receptor proteins that regulate gene expression. Lanifibranor is a PPAR agonist that is designed to target all three PPAR isoforms in a moderately potent manner, with a well-balanced activation of PPARα and PPARδ, and a partial activation of PPARγ. While there are other PPAR agonists that target only one or two PPAR isoforms for activation, lanifibranor is the only pan-PPAR agonist in clinical development for the treatment of NASH. Inventiva believes that lanifibranor’s moderate and balanced pan-PPAR binding profile contributes to the favorable tolerability profile that has been observed in clinical trials and pre-clinical studies to date. The FDA has granted Breakthrough Therapy and Fast Track designation to lanifibranor for the treatment of NASH. About Inventiva Inventiva is a clinical-stage biopharmaceutical company focused on the research and development of oral small molecule therapies for the treatment of patients with NASH (also known as metabolic dysfunction-associated steatohepatitis (MASH)), mucopolysaccharidoses (“MPS”) and other diseases with significant unmet medical need. The Company benefits from a strong expertise and experience in the domain of compounds targeting nuclear receptors, transcription factors and epigenetic modulation. Inventiva is currently advancing one clinical candidate, has a pipeline of two preclinical programs and continues to explore other development opportunities to add to its pipeline. Inventiva’s lead product candidate, lanifibranor, is currently in a pivotal Phase III clinical trial, NATiV3, for the treatment of adult patients with NASH, a common and progressive chronic liver disease for which there are currently no approved therapies. Inventiva’s pipeline also includes odiparcil, a drug candidate for the treatment of adult MPS VI patients. As part of Inventiva’s decision to focus clinical efforts on the development of lanifibranor, it suspended its clinical efforts relating to odiparcil and is reviewing available options with respect to its potential further development. Inventiva is also in the process of selecting an oncology development candidate for its Hippo signaling pathway program. The Company has a scientific team of approximately 90 people with deep expertise in the fields of biology, medicinal and computational chemistry, pharmacokinetics and pharmacology, and clinical development. It owns an extensive library of approximately 240,000 pharmacologically relevant molecules, approximately 60% of which are proprietary, as well as a wholly-owned research and development facility. Inventiva is a public company listed on compartment B of the regulated market of Euronext Paris (ticker: IVA, ISIN: FR0013233012) and on the Nasdaq Global Market in the United States (ticker: IVA). www.inventivapharma.com Contacts Inventiva Pascaline Clerc EVP, Strategy and Corporate Affairs media@inventivapharma.com +1 240 620 9175 Brunswick Group Tristan Roquet Montegon / Aude Lepreux / Matthieu Benoist Media relations inventiva@brunswickgroup.com +33 1 53 96 83 83 Westwicke, an ICR Company Patricia L. Bank Investor relations patti.bank@westwicke.com +1 415 513-1284 Important Notice This press release contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this press release are forward-looking statements. These statements include, but are not limited to, pre-clinical programs and clinical trials, including design, duration, timing, recruitment costs, screening and enrolment for those trials, including the ongoing NATiV3 Phase III clinical trial with lanifibranor in NASH and LEGEND Phase IIa clinial trial, clinical trial data releases and publications, the information, insights and impacts that may be gathered from clinical trials, the potential therapeutic benefits of Inventiva’s product candidates, including lanifibranor and Inventiva’s pipeline and preclinical and clinical development plans, future activities, expectations, plans, growth, potential revenues and prospects of Inventiva. Certain of these statements, forecasts and estimates can be recognized by the use of words such as, without limitation, “believes”, “anticipates”, “expects”, “intends”, “plans”, “seeks”, “estimates”, “may”, “will”, “would”, “could”, “might”, “should”, “designed”, “hopefully”, “target”, “potential’, and “continue” and similar expressions. Such statements are not historical facts but rather are statements of future expectations and other forward-looking statements that are based on management's beliefs. These statements reflect such views and assumptions prevailing as of the date of the statements and involve known and unknown risks and uncertainties that could cause future results, performance or future events to differ materially from those expressed or implied in such statements. Actual events are difficult to predict and may depend upon factors that are beyond Inventiva's control. There can be no guarantees with respect to pipeline product candidates that the clinical trial results will be available on their anticipated timeline, that future clinical trials will be initiated as anticipated, that product candidates will receive the necessary regulatory approvals on their expected timeline, or at all. Actual results may turn out to be materially different from the anticipated future results, performance or achievements expressed or implied by such statements, forecasts and estimates, due to a number of factors, including that Inventiva is a clinical-stage company with no approved products and no historical product revenues, Inventiva has incurred significant losses since inception, Inventiva has a limited operating history and has never generated any revenue from product sales, Inventiva will require additional capital to finance its operations, in the absence of which, Inventiva may be required to significantly curtail, delay or discontinue one or more of its research or development programs or be unable to expand its operations or otherwise capitalize on its business opportunities and may be unable to continue as a going concern, Inventiva's future success is dependent on the successful clinical development, regulatory approval and subsequent commercialization of current and any future product candidates, preclinical studies or earlier clinical trials are not necessarily predictive of future results and the results of Inventiva's clinical trials may not support Inventiva's product candidate claims, Inventiva’s expectations with respect to the changes to the clinical development plan for lanifibranor for the treatment of NASH may not be realized and may not support the approval of a New Drug Application, Inventiva and its partners may encounter substantial delays in their clinical trials or fail to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities, the ability of Inventiva and its partners to recruit and retain patients in clinical studies, enrolment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside Inventiva's and its partners’ control, Inventiva's product candidates may cause adverse drug reactions or have other properties that could delay or prevent their regulatory approval, or limit their commercial potential, Inventiva faces substantial competition and Inventiva’s and its partners’ business, and preclinical studies and clinical development programs and timelines, its financial condition and results of operations could be materially and adversely affected by geopolitical events, such as the conflict between Russia and Ukraine and the Gaza and Israel related sanctions and related impacts and potential impacts on the initiation, enrolment and completion of Inventiva’s and its partners’ clinical trials on anticipated timelines, health epidemics, and macroeconomic conditions, including global inflation, interest rates, uncertain financial markets and disruptions in banking systems. Given these risks and uncertainties, no representations are made as to the accuracy or fairness of such forward-looking statements, forecasts and estimates. Furthermore, forward-looking statements, forecasts and estimates only speak as of the date of this press release. Readers are cautioned not to place undue reliance on any of these forward-looking statements. Please refer to the Universal Registration Document for the year ended December 31, 2022 filed with the Autorité des Marchés Financiers on March 30, 2023, the Annual Report on Form 20-F for the year ended December 31, 2022 filed with the Securities and Exchange Commission on March 30, 2023 and the Company’s half-year report for the period ended June 30, 2023 for other risks and uncertainties affecting Inventiva, including those described from time to time under the caption “Risk Factors”. Other risks and uncertainties of which Inventiva is not currently aware may also affect its forward-looking statements and may cause actual results and the timing of events to differ materially from those anticipated. All information in this press release is as of the date of the release. Except as required by law, Inventiva has no intention and is under no obligation to update or review the forward-looking statements referred to above. Consequently, Inventiva accepts no liability for any consequences arising from the use of any of the above statement. 1 Inventiva-PR-Cusi-Lani-Topline-Results-EN-06132023.pdf (inventivapharma.com) Attachment Inventiva - PR - AASLD Abstracts 2023 - EN - 11062023

Reported Phase 3 data showing eplontersen continued to show improvement in ATTRv-PN through 85 weeks; December 22, 2023 PDUFA date Completed enrollment in donidalorsen OASIS-HAE study and eplontersen CARDIO-TTRansform ATTR-CM study keeping Phase 3 data readouts on track On track to achieve 2023 financial guidance CARLSBAD, Calif., Aug. 9, 2023 /PRNewswire/ -- – Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the "Company"), today reported financial results for the second quarter of 2023. Financial results are summarized below: Financial Highlights Revenue increased for the second quarter and first half of 2023 by 40% and 16% compared to the same periods last year, respectively, driven by significant partner payments Operating expenses increased in the second quarter and first half of 2023 compared to the prior year as planned, reflecting investments in advancing Ionis' pipeline and go-to-market activities for eplontersen, olezarsen and donidalorsen Cash and short-term investments of $2.4 billion as of June 30, 2023 enables continued investments to drive increasing value Well-capitalized balance sheet reflects 2024 convertible note refinancing that extended maturity to 2028 while maintaining a low coupon and retaining the flexibility to mitigate potential equity dilution Reaffirmed 2023 financial guidance "Ionis is creating significant value in 2023 as we successfully execute on our strategy to bring a steady cadence of transformational medicines to the market. Our growing late-stage pipeline now includes eight medicines for 10 indications, highlighted by eplontersen. Based on the strong and consistent data generated to date and an attractive self-administration profile, we expect eplontersen to be an important new medicine for people with ATTRv-polyneuropathy. We also added QALSODY to our commercial portfolio, a breakthrough treatment for people with SOD1-ALS further strengthening Ionis' leadership in RNA-based therapies for neurological diseases," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "In the second half, we expect continued positive momentum including the Phase 3 readout for olezarsen in familial chylomicronemia syndrome and the potential approval of eplontersen for ATTRv-PN in December." Recent Highlights From Commercial Medicines Biogen presented interim data from the Phase 4 RESPOND study of SMA patients demonstrating improved motor function in most participants treated with SPINRAZA who had unmet medical needs after treatment with gene therapy FDA granted Biogen accelerated approval of QALSODY (tofersen), a first-in-class medicine for patients with SOD1-ALS Recent Highlights From Near-Term Commercial Opportunities Reported positive results from the Phase 3 NEURO-TTRansform study in patients with ATTRv-PN showing eplontersen continued to halt neuropathy disease progression and improve quality of life through 85 weeks Completed enrollment of the Phase 3 CARDIO-TTRansform study of eplontersen in patients with ATTR cardiomyopathy, the largest study ever conducted in ATTR-CM; on track for data readout as early as H1:2025 Licensed eplontersen Latin America rights to AstraZeneca Completed enrollment of the Phase 3 OASIS-HAE study of donidalorsen in patients with hereditary angioedema; on track for data readout in H1:2024 Reported positive topline Phase 2 open label extension data of donidalorsen in patients with hereditary angioedema treated for two years Recent Highlights From Partnered Programs Roche advanced IONIS-FB-LRx into Phase 3 development in patients with immunoglobulin A nephropathy GSK presented durable response data from the Phase 2 B-Sure long-term follow-up study of bepirovirsen in complete responder patients from the Phase 2b B-Clear study of patients with HBV Completed enrollment in the Phase 2 GOLDEN study of IONIS-FB-LRx in patients with geographic atrophy AstraZeneca initiated a Phase 2b study of ION839 (AZD2693) targeting PNPLA3 to treat patients with NASH Entered collaboration with Novartis to advance a next generation program targeting Lp(a) for cardiovascular disease Second Quarter 2023 Financial Results "Our results for the first half of the year keep us on track to achieve our 2023 guidance. We continued to generate substantial and sustained revenue, that together with our well-capitalized balance sheet, allows us to continue investing in key opportunities across our business," said Elizabeth L. Hougen, chief financial officer of Ionis. "With three near-term commercial opportunities that have a combined multi-billion-dollar peak sales potential and a steady cadence of medicines poised to follow closely behind, we are positioned to drive substantial revenue growth and long-term value for shareholders." Revenue Ionis' revenue was comprised of the following: Ionis' revenue increased in the second quarter and first half of 2023 compared to the same periods in 2022 because of increased payments from partnered programs. Ionis believes its substantial and sustainable revenue is an important source of funding that supports the Company's investments to bring potentially transformational medicines to the market. Commercial revenue for the second quarter and first half of 2023 included $61 million and $111 million from SPINRAZA royalties, respectively. Global SPINRAZA product sales of $437 million and $880 million were essentially flat for the second quarter and first half of 2023, respectively, compared to the same periods last year reflecting SPINRAZA's resilience against emerging competition. Ionis' commercial revenue in the second quarter and first half of 2023 also included royalties from the U.S. launch of QALSODY. R&D revenue essentially doubled for the second quarter of 2023 and increased more than 35% for the first half of 2023 compared to the same periods in 2022 reflecting the value Ionis' technology is creating as numerous partnered programs advanced. Operating Expenses Ionis' operating expenses increased in the second quarter and first half of 2023 compared to the same periods in 2022, consistent with expectations. As Ionis advanced its robust pipeline, study costs increased as most of the Company's Phase 3 studies were either fully enrolled or approaching full enrollment resulting in higher R&D expenses year over year. Additionally, as Ionis prepares to launch eplontersen, olezarsen and donidalorsen, the Company's SG&A expenses also increased year over year. Balance Sheet As of June 30, 2023, Ionis' cash, cash equivalents and short-term investments increased to $2.4 billion compared to $2.0 billion at December 31, 2022 primarily due to the $500 million Ionis received from Royalty Pharma in January 2023. Ionis' working capital also increased over the same period primarily due to the Company's higher cash and short-term investments balance. In the first quarter of 2023 the Company recorded a long-term liability for future royalties due to Royalty Pharma. In June 2023 Ionis issued $575 million of senior convertible notes due in June 2028 with an interest rate of 1.75%. Ionis used the majority of the proceeds to repurchase $434 million of its 2024 convertible notes. The Company plans to utilize the residual proceeds to settle the 2024 notes that remain outstanding. Webcast Management will host a conference call and webcast to discuss Ionis' second quarter 2023 results at 11:30 a.m. Eastern time on Wednesday, August 9, 2023. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company's second quarter 2023 earnings slides click here. About Ionis Pharmaceuticals, Inc. For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care. Ionis currently has four marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become the leader in genetic medicine, utilizing a multi-platform approach to discover, develop and deliver life-transforming therapies. To learn more about Ionis visit or follow us on Twitter @ionispharma. Ionis' Forward-looking Statement This press release includes forward-looking statements regarding Ionis' business, financial guidance and the therapeutic and commercial potential of QALSODY (tofersen), SPINRAZA (nusinersen), TEGSEDI (inotersen), WAYLIVRA (volanesorsen), eplontersen, olezarsen, donidalorsen, ulefnersen, pelacarsen, bepirovirsen, IONIS-FB-LRx, Ionis' technologies and Ionis' other products in development. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Ionis. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis' programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2022, and most recent Form 10-Q, which are on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company. In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. Akcea Therapeutics® is a registered trademark of Akcea Therapeutics, Inc. TEGSEDI® is a registered trademark of Akcea Therapeutics, Inc. WAYLIVRA® is a registered trademark of Akcea Therapeutics, Inc. QALSODYTM is a trademark of Biogen. SPINRAZA® is a registered trademark of Biogen. Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis' non-GAAP results is consistent with how Ionis' management internally evaluates the performance of its operations. 2023 Key Value Driving Events(1) SOURCE Ionis Pharmaceuticals, Inc.

Conference Call and Webcast Today, May 2, 2023 at 4:30 p.m. ET PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced financial results for its fiscal second quarter ended March 31, 2023. The company is hosting a conference call today, May 2, 2023, at 4:30 p.m. ET to discuss the results. Webcast and Conference Call and Details Investors may access a live audio webcast on the Company's website at . A replay of the webcast will be available approximately two hours after the conclusion of the call. For analysts that wish to participate in the conference call, please register at . Once registered, you will receive the dial-in number and a personalized PIN code that will be required to access the call. Selected Recent Events Reported interim results from an ongoing Phase 1/2 clinical study of ARO-RAGE, an investigational RNAi therapeutic for treatment for inflammatory pulmonary diseases, such as asthma. These data represent the first clinical demonstration of the potential utility of Arrowhead’s proprietary Targeted RNAi Molecule (TRiMTM) platform optimized for delivery to the lungs. Key results from Part 1 of the study in normal healthy volunteers included the following: Mean maximum reduction in soluble RAGE (sRAGE) as measured in serum after two doses of 92 mg on Day 1 and Day 29 was 80% with a maximum reduction of 90% Duration of pharmacologic effect persisted for at least 6 weeks Mean reduction in sRAGE as measured in bronchoalveolar lavage fluid (BALF) at Day 31 after a single dose of 92 mg was 75% with a maximum reduction of 92% Mean maximum reduction of 56% with a maximum reduction of 68% in serum sRAGE was also observed after a single dose of 92 mg Safety and tolerability Overall, no patterns of adverse changes in any clinical safety parameters No reported serious or severe adverse events No dropouts related to drug or related to adverse events These results include 4 of 5 escalating dose levels. Data are not yet available for single or multiple dose cohorts at 184 mg, the highest dose being tested Announced a planned R&D Day on June 1, 2023, which will include presentations on cardiometabolic, pulmonary, and newly announced central nervous system (CNS) pipeline programs The company expanded its TRiMTM platform to include an optimized intrathecal administration for CNS delivery with good distribution throughout the brain and in all relevant brain cell types. The first development candidate to utilize this new delivery platform, ARO-SOD1, is on track for a clinical trial application filing in the third quarter of 2023 to begin clinical studies In preclinical studies, ARO-SOD1 achieved 95% spinal cord tissue mRNA knockdown after a single intrathecal dose in human SOD1 transgenic rats and maintained greater than 80% spinal cord tissue mRNA knockdown three months after a single intrathecal dose in non-human primates Earned a $40 million milestone payment from Takeda (TSE:4502/NYSE:TAK) after the first patient was dosed in the Phase 3 REDWOOD clinical study of fazirsiran (TAK-999/ARO-AAT) for the treatment of alpha-1 antitrypsin deficiency associated liver disease (AATD-LD) Received Fast Track designation from the U.S. Food and Drug Administration (FDA) for ARO-APOC3 for reducing triglycerides in adult patients with familial chylomicronemia syndrome Earned a $30 million milestone payment from GSK (LSE/NYSE: GSK) following the start of GSK’s Phase 2b trial of GSK4532990, formerly called ARO-HSD, an investigational RNAi therapeutic for the treatment of patients with non-alcoholic steatohepatitis (NASH) Initiated dosing in a Phase 1/2a single ascending dose and multiple ascending dose clinical study of ARO-MMP7, Arrowhead’s third pulmonary targeted investigational RNAi therapeutic being developed as a potential treatment for idiopathic pulmonary fibrosis Reported interim results from an ongoing Phase 1/2 clinical study of ARO-C3, an investigational RNAi therapeutic for treatment of various complement mediated diseases, demonstrating mean reductions of 88% in C3 and 91% in AH50, a marker of alternative complement pathway hemolytic activity Regained rights to ARO-PNPLA3, formerly called JNJ-75220795, which was part of a 2018 research collaboration and option agreement between Arrowhead and Janssen Pharmaceuticals, Inc. ARO-PNPLA3 is an investigational RNAi therapeutic developed using Arrowhead’s proprietary TRiMTM platform and designed to reduce liver expression of patatin-like phospholipase domain containing 3 (PNPLA3) as a potential treatment for patients with NASH Announced topline results with Takeda from the Phase 2 SEQUOIA clinical study of investigational fazirsiran for the treatment of AATD-LD and provided an outline of a Phase 3 study that was co-developed by Takeda and Arrowhead and will be conducted by Takeda. Key results from SEQUOIA included the following: Fibrosis regression observed in 50% of patients receiving fazirsiran Median reductions of 94% of Z-AAT accumulation in the liver and mean reduction of 68% in histologic globule burden Treatment emergent adverse events were generally well balanced between fazirsiran and placebo groups Results consistent with AROAAT-2002 open-label study previously published in The New England Journal of Medicine Selected Fiscal 2023 Second Quarter Financial Results Three Months Ended March 31, OPERATING SUMMARY 2023 2022 (unaudited) Revenue $ 146,267 $ 151,805 Operating Expenses: Research and development 74,881 75,985 General and administrative expenses 23,221 34,267 Total Operating Expenses 98,102 110,252 Operating income 48,165 41,553 Interest income 4,560 1,054 Interest expense (5,067 ) - Other, net 8 1,759 Income before income tax expense and noncontrolling interest 47,676 44,366 Income tax expense - - Net income before noncontrolling interest 47,676 44,366 Net loss attributable to noncontrolling interest, net of tax (999 ) - Net income attributable to Arrowhead Pharmaceuticals, Inc. $ 48,675 $ 44,366 Net income per share attributable to Arrowhead Pharmaceuticals, Inc. - Diluted $ 0.45 $ 0.41 Weighted-average shares used in calculating - Diluted 108,143 107,929 FINANCIAL POSITION SUMMARY March 31, 2023 September 30, 2022 (unaudited) Cash, cash equivalents and restricted cash $ 134,959 $ 108,005 Short-term investments 346,046 268,391 Long-term investments 78,834 105,872 Total cash resources (cash and investments) 559,839 482,268 Other assets 331,469 209,671 Total Assets $ 891,308 $ 691,939 Current deferred revenue $ 29,839 $ 74,099 Long-term deferred revenue 1,075 55,950 Other liabilities 395,288 143,551 Total Liabilities $ 426,202 $ 273,600 Total Arrowhead Pharmaceuticals, Inc. Stockholders' Equity $ 446,772 $ 398,520 Noncontrolling Interest 18,334 19,819 Total Noncontrolling Interest and Stockholders' Equity 465,106 418,339 Total Liabilities, Noncontrolling Interest and Stockholders' Equity $ 891,308 $ 691,939 Shares Outstanding 106,869 105,960 About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. For more information, please visit , or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit . Safe Harbor Statement under the Private Securities Litigation Reform Act: This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as “may,” “will,” “expect,” “believe,” “anticipate,” “hope,” “intend,” “plan,” “project,” “could,” “estimate,” “continue,” “target,” “forecast” or “continue” or the negative of these words or other variations thereof or comparable terminology are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline or product candidates, including anticipated regulatory submissions and clinical program results, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements include, but are not limited to, statements about the initiation, timing, progress and results of our preclinical studies and clinical trials, and our research and development programs; our expectations regarding the potential benefits of the partnership, licensing and/or collaboration arrangements and other strategic arrangements and transactions we have entered into or may enter into in the future; our beliefs and expectations regarding milestone, royalty or other payments that could be due to or from third parties under existing agreements; and our estimates regarding future revenues, research and development expenses, capital requirements and payments to third parties. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, decisions of regulatory authorities and the timing thereof, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc. View source version on businesswire.com: Contacts Arrowhead Pharmaceuticals, Inc. Vince Anzalone, CFA 626-304-3400 ir@arrowheadpharma.com Investors: LifeSci Advisors, LLC Brian Ritchie 212-915-2578 britchie@lifesciadvisors.com Media: LifeSci Communications, LLC Jason Braco, Ph.D. 646-751-4361 jbraco@lifescicomms.com Source: Arrowhead Pharmaceuticals, Inc. View this news release online at: