APOC3

CARLSBAD, Calif., Feb. 15, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug designation to the investigational medicine olezarsen for the treatment of familial chylomicronemia syndrome (FCS), a rare, genetic disease characterized by extremely elevated triglyceride levels and recurrent acute pancreatitis (AP). The FDA grants Orphan Drug designation to therapies intended for treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the U.S. at the time of designation. "People living with FCS are in urgent need of a medicine that may help stabilize their triglyceride levels and reduce the risk of life-threatening AP attacks," said Sam Tsimikas, M.D., senior vice president, global cardiovascular development of Ionis. "If approved, olezarsen has the potential to be the standard of care in the U.S. for the treatment of FCS. We are deeply committed to advancing this important medicine that has the potential to be transformative for people and families living with FCS." FCS prevents the body from breaking down fats, which can result in fasting triglyceride levels that can range from 10 to 100 times higher than normal levels.1,2 People with FCS are at high risk of AP, or inflammation of the pancreas, which often results in hospitalization and can be life-threatening.3 In severe cases, vital organs such as the heart, lungs, kidneys and pancreas can be damaged.4 Under the FDA's Orphan Drug Act, orphan drug status provides incentives, including tax credits, grants and waiver of certain administrative fees for clinical trials, and seven years of market exclusivity following drug approval. About Olezarsen Olezarsen is an RNA-targeted investigational LIgand Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood. The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials. About FCS FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL). Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides. FCS is estimated to impact one to two people per million worldwide. People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain. People living with FCS are sometimes unable to work, adding to the burden of disease. Currently, there are no U.S. FDA-approved therapies for the treatment of FCS and standard triglyceride lowering therapies are generally ineffective in patients with FCS. People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to adhere to diets to navigate the health risks associated with FCS. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn. Forward-looking Statements This press release includes forward-looking statements regarding olezarsen, Ionis' business, and the therapeutic and commercial potential of Ionis' commercial medicines, additional medicines in development and technologies. 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 but not limited to those related to our commercial products and the medicines in our pipeline, and particularly 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 Dec. 31, 2022, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® is a registered trademark of Ionis Pharmaceuticals, Inc. 1 Pallazola et al. Eur J Preventive Cardiol 2020 27:2276-2278. 2 Gaudet D, et al. N Engl J Med. 2014;371:2200-2206. 3 Chyzhyk V, Brown AS. Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis. Trends Cardiovasc Med. 2020;30(2):80-5. 4 "Pancreatitis." WebMD. . SOURCE Ionis Pharmaceuticals, Inc.

- Conference Call and Webcast Today, November 29, 2023, at 4:30 p.m. ET PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc., (NASDAQ: ARWR) today announced financial results for its fiscal year ended September 30, 2023. The company is hosting a conference call today, November 29, 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 Presented new Phase 2 clinical data from the ongoing SHASTA-2 and MUIR studies of plozasiran (ARO-APOC3) and the ARCHES-2 study of zodasiran (ARO-ANG3) at the American Heart Association (AHA) Scientific Sessions. Key updates included: Plozasiran achieved mean max reductions of up to 90% in APOC3, 87% in triglycerides, and 63% in remnant cholesterol in patients with severe hypertriglyceridemia. In patients with mixed dyslipidemia, plozasiran achieved a mean max reduction in APOC3 of up to 89%, leading to robust and durable improvements in multiple atherogenic lipoproteins Zodasiran treatment resulted in substantial reductions of ANGPTL3, triglycerides, and LDL-cholesterol in patients with mixed dyslipidemia Plozasiran and zodasiran continue to show favorable safety pro Treatment emergent adverse events reported to date reflect the comorbidities and underlying conditions of the study populations Hosted a webinar featuring experts in the treatment and management of lipid and lipoprotein disorders to discuss plozasiran Daniel Gaudet, MD, PhD, Professor of Medicine at Université de Montréal, discussed plozasiran in the context of the current treatment landscape for severe hypertriglyceridemia Børge Nordestgaard, MD, Professor & Chief Physician, Copenhagen University Hospital, University of Copenhagen, Denmark, discussed the emergent role of remnant cholesterol in cardiovascular disease Steven Nissen, MD, Chief Academic Officer for the Heart and Vascular Institute at the Cleveland Clinic, discussed why the decrease in atherogenic lipoproteins observed with plozasiran has the potential to prevent cardiovascular outcomes Completed chronic GLP toxicology for pulmonary candidates ARO-RAGE, designed to reduce expression of the receptor for advanced glycation end products as a potential treatment for inflammatory pulmonary diseases, and ARO-MMP7, designed to reduce expression of matrix metalloproteinase 7 as a potential treatment for idiopathic pulmonary fibrosis Results were highly encouraging and suggest sufficient safety margins to proceed to Phase 2 studies Presented data on the company’s pipeline of pulmonary targeted RNAi therapeutic candidates, including clinical results for ARO-RAGE, at the European Respiratory Society (ERS) International Congress 2023. Key results included: Late-breaking clinical data for ARO-RAGE demonstrated deep and durable gene silencing in healthy volunteers and in patients with asthma Promising preclinical data across multiple pulmonary programs suggested broad potential applications for Arrowhead’s TRiM™ platform Filed for regulatory clearance to initiate a Phase 1/2a study of Arrowhead’s second RNAi therapeutic candidate targeting skeletal muscle, ARO-DM1, for patients with type 1 myotonic dystrophy Announced that GSK plc reached an agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company, to transfer exclusive worldwide rights to further develop and commercialize JNJ-3989. JNJ-3989 (formerly ARO-HBV) was initially in-licensed by Janssen from Arrowhead in 2018 Selected Fiscal 2023 Year End Financial Results ARROWHEAD PHARMACEUTICALS, INC. CONSOLIDATED CONDENSED FINANCIAL INFORMATION (in thousands, except per share amounts) OPERATING SUMMARY Year Ended September 30, 2023 2022 Revenue $ 240,735 $ 243,231 Operating Expenses: Research and development 353,188 297,307 General and administrative expenses 92,549 124,431 Total Operating Expenses 445,737 421,738 Operating loss (205,002 ) (178,507 ) Interest income 15,299 5,033 Interest expense (18,326 ) - Other, net 1,538 765 Loss before income tax expense and noncontrolling interest (206,491 ) (172,709 ) Income tax expense 2,784 3,785 Net loss including noncontrolling interest (209,275 ) (176,494 ) Net loss attributable to noncontrolling interest, net of tax (4,000 ) (431 ) Net loss attributable to Arrowhead Pharmaceuticals, Inc. $ (205,275 ) $ (176,063 ) Net loss per share attributable to Arrowhead Pharmaceuticals, Inc. - Diluted $ (1.92 ) $ (1.67 ) Weighted-average shares used in calculating - Diluted 106,750 105,426 FINANCIAL POSITION SUMMARY September 30, 2023 2022 Cash, cash equivalents and restricted cash $ 110,891 $ 108,005 Investments 292,735 374,263 Total cash resources (cash and investments) 403,626 482,268 Other assets 361,926 209,671 Total Assets $ 765,552 $ 691,939 Current deferred revenue $ 866 $ 74,099 Long-term deferred revenue - 55,950 Other liabilities 477,524 143,551 Total Liabilities $ 478,390 $ 273,600 Total Arrowhead Pharmaceuticals, Inc. Stockholders' Equity $ 271,343 $ 398,520 Noncontrolling Interest 15,819 19,819 Total Noncontrolling Interest and Stockholders' Equity $ 287,162 $ 418,339 Total Liabilities, Noncontrolling Interest and Stockholders' Equity $ 765,552 $ 691,939 Shares Outstanding 107,312 105,960 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.

- Plozasiran achieved mean max reductions of up to 90% in APOC3 and 87% in triglycerides in patients with severe hypertriglyceridemia - In patients with mixed dyslipidemia, mean max reduction in APOC3 was up to 89% leading to robust and durable reductions in multiple atherogenic lipoproteins - Company will host a virtual analyst and investor event today, November 13, 2023, at 4:30 pm ET PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today presented new Phase 2 clinical data from the ongoing SHASTA-2 and MUIR studies of plozasiran (ARO-APOC3) and the ARCHES-2 study of zodasiran (ARO-ANG3) at the American Heart Association (AHA) Scientific Sessions 2023, being held in Philadelphia, PA, on November 11-13, 2023. “The compelling data presented today at AHA support the further development of plozasiran in Phase 3 studies, including in patients with severe hypertriglyceridemia (SHTG), and potentially in a clinical outcomes trial for patients with increased risk for atherosclerotic cardiovascular disease (ASCVD) due to elevated triglyceride rich lipoproteins (TRLs),” said Christie M. Ballantyne, M.D., Baylor College of Medicine. “Numerous epidemiologic studies have shown an association between higher TRLs and an increased risk of ASCVD. Despite potent LDL-C lowering therapies, residual ASCVD risk persists due in part to high levels of atherogenic TRLs. Importantly, plozasiran is the first investigational RNAi-based molecule to demonstrate substantial reductions in TRLs in a mixed dyslipidemia population.” Plozasiran Data In the Phase 2 SHASTA-2 study of plozasiran in 226 subjects with SHTG who had baseline triglycerides (TGs) of greater than 500 mg/dL, two doses of 10 mg, 25 mg, or 50 mg of plozasiran once every 12 weeks reduced TGs to near normal levels and achieved TG levels below the risk threshold for acute pancreatitis (less than 500 mg/dL) in over 90% of patients. At 24 weeks, plozasiran durably decreased serum APOC3 to -79%, TGs to -74%, and remnant cholesterol to -63%, while increasing HDL-cholesterol to +68%. Plozasiran continues to show a favorable safety pro date. Treatment emergent adverse events (TEAEs) reported to date reflect the comorbidities and underlying conditions of the study population. Serious TEAEs were not related to plozasiran and were resolved without sequelae, except two subjects with malignancies. In the Phase 2 MUIR study of plozasiran in 353 subjects with mixed dyslipidemia who had fasting TGs between 150-499 mg/dL and either LDL-cholesterol greater than 70 mg/dL or non-HDL-cholesterol greater 100 mg/dL, two doses of 10 mg, 25 mg, or 50 mg of plozasiran once every 12 weeks or once every 24 weeks silenced APOC3 and demonstrated robust reductions in atherogenic lipoproteins. At 24 weeks, plozasiran reduced TGs to -64%, remnant cholesterol to -54%, apolipoprotein B (ApoB) to -19%, and Non-HDL-cholesterol to -27%, while increasing HDL-cholesterol to +51%. TEAEs reported to date reflect the comorbidities and underlying conditions of the study population. Most serious TEAEs recovered with no sequelae. Details about the AHA presentations are listed below. Title: ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces Triglycerides to Near Normal Levels in Patients With Severe Hypertriglyceridemia: SHASTA-2 Study Results Date/Time: November 13, 2023, 9:45 a.m. EST Presenter: Daniel Gaudet Session: Lipid Lowering via Novel Pathways Title: ARO-APOC3, an Investigational RNAi Therapeutic, Silences APOC3 and Reduces Atherosclerosis-Associated Lipoproteins in Patients With Mixed Dyslipidemia: MUIR Study Results Date/Time: November 13, 2023, 1:30 p.m. EST Presenter: Christie M Ballantyne Session: Emerging Approaches to Lipid Lowering Zodasiran Data In the Phase 2 ARCHES-2 study of zodasiran in 204 subjects with mixed dyslipidemia who had fasting TGs between 150-499 mg/dL and either LDL-cholesterol greater than 70 mg/dL or non-HDL-cholesterol greater 100 mg/dL, two doses of 50 mg, 100 mg, or 200 mg of zodasiran once every 12 weeks silenced the expression of angiopoietin-like protein 3 (ANGPTL3) and decreased atherogenic lipoproteins. Treatment with zodasiran resulted in substantial reductions of ANGPTL3 up to -71% at week 8, TGs up to 59% at week 16, and LDL-C up to -32% at week 16. ARO-ANG3 was also associated with a relative reduction in liver fat fraction at week 24, with no adverse events related to liver function test changes reported to date. ARO-ANG3 TEAEs reported to date are consistent with those expected in this patient population and with associated underlying comorbidities. Details about the AHA presentation are listed below. Title: ARO-ANG3, an Investigational RNAi Therapeutic, Silences the Expression of ANGPTL3 and Decreases Atherogenic Lipoproteins in Patients With Mixed Dyslipidemia: ARCHES-2 Study Results Date/Time: November 13, 2023, 1:30 p.m. EST Presenter: Robert S Rosenson Session: Emerging Approaches to Lipid Lowering Virtual Analyst and Investor Event The company is hosting a virtual analyst and investor event today, November 13, 2023, at 4:30 pm ET featuring key opinion leaders who will discuss the plozasiran data and its potential as a treatment for SHTG and mixed dyslipidemia in patients with ASCVD. To register for the event, please visit: . The analyst and investor event will feature presentations from Arrowhead management and three experts in the treatment and management of lipid and lipoprotein disorders: Daniel Gaudet, MD, PhD, Professor of Medicine at Université de Montréal, who will discuss plozasiran in the context of the current treatment landscape for severe hypertriglyceridemia Børge Nordestgaard, MD, Professor & Chief Physician, Copenhagen University Hospital, University of Copenhagen, Denmark, who will discuss remnant cholesterol and its role in cardiovascular disease Steven Nissen, MD, Chief Academic Officer for the Heart and Vascular Institute at the Cleveland Clinic, who will discuss the potential of a cardiovascular outcomes study of plozasiran A copy of the presentation materials and a webcast link for the analyst and investor event will be available on the Events and Presentations page under the Investors section of the Arrowhead website. 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.