Craniofacial Abnormalities

– Olezarsen met the primary endpoint with statistically significant reduction of fasting triglycerides and showed substantial, clinically meaningful reduction in acute pancreatitis events – – Results demonstrate olezarsen may represent a novel treatment option for this rare, life-threatening disease, for which there are no approved treatments in the U.S. – – Data presented today at ACC 2024 and published in The New England Journal of Medicine – – Ionis to host webcast on Monday, April 8 at 10:00 am ET – CARLSBAD, Calif., April 7, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced full results from the Phase 3 Balance study of Ionis' lead independent investigational medicine, olezarsen, for the treatment of adults with familial chylomicronemia syndrome (FCS). The olezarsen 80 mg monthly dose met the primary endpoint of significantly reducing triglycerides (TGs) in patients with genetically validated FCS at six months. In addition, olezarsen demonstrated robust and sustained reductions in TGs and serum apolipoprotein C-III (apoC-III) levels. Importantly, olezarsen reduced the incidence of acute pancreatitis (AP) events over the 12-month treatment period compared to placebo. Olezarsen also demonstrated a favorable safety and tolerability profile. These results were presented in an oral presentation at the 2024 American College of Cardiology (ACC) Annual Meeting in Atlanta, Georgia and published simultaneously in The New England Journal of Medicine (NEJM). Based on these data, Ionis is pursuing regulatory approval of olezarsen as a potential breakthrough treatment for adults with FCS. "As a physician who has seen first-hand the struggles of people living with FCS and its serious complications, there is significant need for an effective therapy to lower triglycerides and reduce acute pancreatitis events," said Erik Stroes, M.D., professor of medicine, Amsterdam University Medical Centers, and a principal investigator of the Balance study. "Olezarsen represents a potentially life-changing new medicine for these patients who experience debilitating chronic symptoms, including abdominal pain and cognitive symptoms, as well as hospitalizations associated with potentially fatal acute pancreatitis events." Balance Study Results In the study, patients were treated with olezarsen 80 mg (n=22), 50 mg (n=21) or placebo (n=23) once every four weeks. In the 80 mg group, olezarsen met the primary endpoint, with a statistically significant placebo-adjusted reduction in TG levels from baseline to six months (44%, p<0.001). Reductions from six to 12 months were sustained, with olezarsen 80 mg achieving a placebo-adjusted 59% reduction in TGs. ApoC-III placebo-adjusted reductions were robust and sustained at six and 12 months (74% and 81% reductions, respectively). In the 50 mg group, olezarsen reduced TG levels, however this difference was not statistically significant at six months compared to placebo (22%, p=0.078). Reductions from six to 12 months were improved, with olezarsen 50 mg achieving a placebo-adjusted 44% reduction in TGs. Olezarsen-treated patients had markedly fewer AP events during the 12-month period, compared to placebo. Eleven episodes of AP occurred in the placebo group versus one episode in the 80 mg olezarsen group and one episode in the 50 mg group. Furthermore, there was a substantially greater time to the first event with olezarsen compared to placebo (one year (80 mg) and 102 days (50 mg), vs. nine days for placebo). Olezarsen-treated patients experienced a placebo-adjusted 84% reduction in all-cause hospitalizations between baseline and 12 months. A favorable safety and tolerability profile was observed, with a higher number of treatment-emergent adverse events (TEAEs) in the placebo group. There were no serious TEAEs related to olezarsen. The most common AEs were COVID-19, abdominal pain and diarrhea, none of which were more frequent in patients treated with either dose of olezarsen versus placebo. Serious AEs occurred in 14% of patients treated with olezarsen 80 mg, 19% treated with olezarsen 50 mg, and 39% treated with placebo. "Balance is the first clinical study to validate the association of reduced triglyceride levels with reduced incidence of acute pancreatitis events in patients with severely elevated triglycerides. This important finding supports the potential for olezarsen to be the standard of care for patients with FCS, if approved. These data further strengthen our confidence for a successful outcome in the ongoing Phase 3 CORE studies evaluating olezarsen in the much more prevalent severe hypertriglyceridemia patient population," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "Our team looks forward to working closely with the FDA to advance the first potential treatment for FCS in the U.S., and to successfully delivering Ionis' first independent commercial launch later this year, assuming priority review. We offer our sincerest gratitude to the patients and investigators who participated in this pivotal study." The ACC Balance presentation can be found on Ionis' website after today's presentation at 10:08 am ET. In addition to the Balance data, a late-breaking abstract entitled, "Efficacy and Safety of Olezarsen in Patients with Hypertriglyceridemia and High Cardiovascular Risk: Primary Results of the Bridge-TIMI 73a Trial" was also presented at ACC and published in NEJM. Webcast Ionis will host a webcast to discuss the detailed results from the Balance study on Monday, April 8 at 10:00 am ET. Interested parties may access the webcast here. A webcast replay will be available for a limited time. About the Balance Study The global, multicenter, randomized, double-blind, placebo-controlled Phase 3 Balance study (NCT04568434) enrolled 66 patients aged 18 and older with confirmed FCS. Patients in the study received background therapies including statins, fibrates and omega-3 fatty acids. Patients were randomized in a 1:1:1 ratio to receive olezarsen 80 mg or 50 mg or placebo via subcutaneous injection once every four weeks for 53 weeks. The primary endpoint was the percent change from baseline in fasting triglyceride levels at six months compared to placebo. Secondary endpoints included percent changes in triglyceride levels at 12 months, percent changes in other lipid parameters, and adjudicated acute pancreatitis event rates over the treatment period. 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.1,2 The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023, as well as Orphan Drug designation and Breakthrough Therapy designation in February 2024. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials. Olezarsen is an investigational medicine that has not been reviewed or approved for the treatment of any disease by any regulatory authority. 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).3 Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides.3,4 FCS is estimated to impact one to 13 people per million in the U.S.5,6,7 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.3,8,9 People living with FCS are sometimes unable to work, adding to the burden of disease.9 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.10,11 People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to manage diets to navigate the health risks associated with FCS.11,12 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. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. 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, 2023, 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. Ionis Pharmaceuticals Investor Contact: D. Wade Walke, Ph.D. - [email protected] - 760-603-2331; Ionis Pharmaceuticals Media Contact: Hayley Soffer - [email protected] - 760-603-4679 1Alexander VJ, et al. Eur Heart J 2019;40(33):2785-2796. 2Tardif JC, et al. Eur Heart J 2022;43(14):1401-1412. 3Gaudet D, et al. N Engl J Med. 2014;371:2200-2206. 4Ginsberg HN, et al. Eur Heart J. 2021;42:4791-4806. 5Pallazola VA, et al. Eur J Prev Cardiol 2020;27(19):2276-8. 6Warden BA, et al. J Clin Lipidol 2020;14(2):201-6. 7Tripathi M, et al. Endocr Pract 2021;27(1):71-6. 8Bashir B, et al. Metabolites. 2023;(5):621. 9Davidson M, et al. J Clin Lipidol. 2018;12(4):898-907.e2. 10Gouni-Berthold I. J Endocr Soc. 2019;4(2):bvz035. 11Paquette M, et al. Atherosclerosis. 2019;283:137-142. 12Williams L, et al. J Clin Lipidol. 2018;4:908-919. SOURCE Ionis Pharmaceuticals, Inc.

Pictured: 3D illustration of arrows reflecting changes in direction/iStock/Olivier Le Moal Despite having an FDA-approved product, Gamida Cell is entering into a restructuring agreement in which it will become a private company under the ownership of Highbridge Capital Management amid financial struggles, the company announced Wednesday. Under the agreement, Gamida Cell will become a private company wholly owned by Highbridge Capital Management—the biotech’s principal lender. The move is designed to give the company some long-term runway and support the commercialization of Omisirge, an FDA-approved nicotinamide modified allogeneic hematopoietic progenitor cell therapy. This comes after the biotech announced in January that it was seeking “strategic alternatives” and was focused on an asset sale, merger, or other deal. “In March 2023, Gamida Cell embarked on an extensive strategic process to address its capital structure and liquidity constraints by partnering Omisirge with a third party,” Gamida Cell CEO Abbey Jenkins said in Wednesday’s statement. “Unfortunately, that process did not yield any actionable alternatives. This restructuring will enable Gamida Cell to remain a going concern. It will support our ongoing efforts to make Omisirge available to more transplant centers and their patients as a potentially lifesaving donor source option.” The terms of the restructuring will see Highbridge convert $75 million of its existing unsecured convertible senior note into equity for Gamida Cell. The biotech will also get $30 million of new capital from Highbridge when the restructuring goes into effect. The biotech will now be off the stock market and wholly owned by Highbridge, with all ordinary shares expected to be canceled. The reorganized Gamida Cell will also issue contingent value rights with a maximum value of $27.5 million to shareholders. Gamida Cell’s main product, Omisirge, was approved by the FDA in April 2023 after a lengthy regulatory road and is indicated for patients who are scheduled to undergo umbilical cord blood transplantation after chemotherapy or radiotherapy. However, the therapy does come with a boxed warning for potentially fatal conditions such as infusion reactions, graft failure, engraftment syndrome, and graft-versus-host disease. The company revealed in a third-quarter report in 2023 that 17 transplant centers were onboarded to provide Omisirge to patients, exceeding the company’s target of 10 to 15. However, the company said that it would continue to have a “lean launch effort” in 2024 due to “resource constraints” and—contingent on additional funding to extend its cash runway—would plan to onboard at least 40 transplant centers by the end of this year. “Despite Gamida Cell’s financial struggles, we believe in the potential of Omisirge to fulfill an important unmet need in stem cell transplant,” Jonathan Segal, co-chief investment officer at Highbridge Capital Management, said in a statement. “Subject to an approved budget from the Company’s new board of directors, we intend to provide the Company with additional capital to fund this potentially life-saving therapy.” The deal is expected to close in the second quarter of 2024 upon being approved by an Israeli court. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Call Scheduled for Today, Thursday, March 28, 2024 at 5:00 pm ETLITTLETON, Colo., March 28, 2024 (GLOBE NEWSWIRE) -- Vivos Therapeutics, Inc. (“Vivos” or the “Company”) (NASDAQ: VVOS), a leading medical device and technology company specializing in the development and commercialization of highly effective proprietary treatments for sleep related breathing disorders (including all severities of obstructive sleep apnea (OSA in adults)), today announced it plans to release its fourth quarter and full year 2023 financial results after market close today, Thursday, March 28, 2024. The Company will conduct a conference call today at 5:00 p.m. (Eastern Time) to review the results and provide an overview of the Company’s recent milestones and developments. To access Vivos’ investor conference call, please dial (888) 886-7786, or for international callers, (416) 764-8658. A replay will be available shortly after the call and can be accessed by dialing (844) 512-2921, or for international callers, (412) 317-6671. The passcode for the live call and the replay is 27185528. The replay will be available until April 11, 2024. A live webcast of the conference call can be accessed on Vivos’ website at https://vivos.com/investor-relations. An online archive of the webcast will be available on the Company’s website for 30 days following the call. About Vivos Therapeutics, Inc. Vivos Therapeutics, Inc. (NASDAQ: VVOS) is a medical technology company focused on developing and commercializing innovative diagnostic and treatment methods for patients suffering from breathing and sleep issues arising from certain dentofacial abnormalities such as obstructive sleep apnea (OSA) and snoring in adults. The Vivos Method represents the first clinically effective nonsurgical, noninvasive, nonpharmaceutical and cost-effective solution for treating adult mild to severe OSA. It has proven effective in over 42,000 patients treated worldwide by more than 1,900 trained dentists. The Vivos Method includes treatment regimens that employ proprietary appliance therapy and other modalities that alter the size, shape and position of the soft tissues that comprise a patient’s upper airway and/or palate. The Vivos Method opens airway space and may significantly reduce symptoms and conditions associated with adult mild-to-severe OSA, such as lowering Apnea Hypopnea Index scores. Vivos also markets and distributes SleepImage diagnostic technology under its VivoScore program for home sleep testing in adults and children. The Vivos Integrated Practice (VIP) program offers dentists training and other value-added services in connection with using The Vivos Method. Cautionary Note Regarding Forward-Looking Statements This press release, the conference call referred to herein, and statements of the Company’s management made in connection therewith contain “forward-looking statements” (as defined in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended) concerning future events. Words such as “may”, “should”, “expects”, “projects,” “intends”, “plans”, “believes”, “anticipates”, “hopes”, “estimates”, “goal” and variations of such words and similar expressions are intended to identify forward-looking statements. These statements involve significant known and unknown risks and are based upon several assumptions and estimates, which are inherently subject to significant uncertainties and contingencies, many of which are beyond Vivos’ control. Actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause actual results to differ materially include, but are not limited to: (i) the risk that Vivos may be unable to implement revenue, sales and marketing strategies and other strategies that increase revenues, (ii) the risk that some patients may not achieve the desired results from using Vivos products, (iii) risks associated with regulatory scrutiny of and adverse publicity in the sleep apnea treatment sector; (iv) the risk that Vivos may be unable to secure additional financing on reasonable terms when needed, if at all, or maintain its Nasdaq listing and (v) other risk factors described in Vivos’ filings with the SEC. Vivos’ filings can be obtained free of charge on the SEC’s website at www.sec.gov. Except to the extent required by law, Vivos expressly disclaims any obligations or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Vivos’ expectations with respect thereto or any change in events, conditions, or circumstances on which any statement is based. Vivos Investor Relations and Media Contact:Julie GannonInvestor Relations Officer720-442-8113jgannon@vivoslife.com