Ligand Pharmaceuticals, Inc.

– 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.

Pharmaceutical executive Scott Plesha named CEO Lead product ZELSUVMI expected to be commercially available in late 2024 JUPITER, Fla. & DURHAM, N.C.--(BUSINESS WIRE)-- Ligand Pharmaceuticals Inc. (Nasdaq: LGND) today announced the launch of Pelthos Therapeutics (Pelthos), a biopharmaceutical company, and the appointment of seasoned industry executive Scott Plesha to the role of Chief Executive Officer. This press release features multimedia. View the full release here: Scott Plesha, CEO, Pelthos Therapeutics (Photo: Business Wire) Pelthos is committed to commercializing innovative, safe, and efficacious therapeutic products to help patients impacted by diseases with limited treatment options. The company’s lead product is ZELSUVMI™ (berdazimer) topical gel, 10.3%, for the treatment of molluscum contagiosum (molluscum) in adults and pediatric patients one year of age and older.1 ZELSUVMI has received a Novel Drug designation from the U.S. Food and Drug Administration and is the first and only approved topical prescription medication that can be applied by patients, parents, or caregivers at home, outside of a physician's office, or other medical setting to treat this highly contagious viral skin infection. The product was developed using Pelthos’ proprietary nitric oxide-based technology platform, NITRICIL™. ZELSUVMI is expected to be available in the United States in late 2024. Ligand acquired the rights to ZELSUVMI and all the assets related to the NITRICIL technology platform from Novan, Inc. in September 2023. “ZELSUVMI is a highly differentiated product that we believe will bring significant improvements to the lives of patients living with tremendous unmet needs,” said Todd Davis, CEO of Ligand. “We are excited for the launch of Pelthos, the commercialization of ZELSUVMI, and the advancement of the company under Scott’s leadership.” Mr. Plesha brings to his role more than 30 years of experience in the pharmaceutical industry, including two decades building and leading specialty pharmaceutical commercial organizations. Prior to joining Pelthos, Mr. Plesha was President and Chief Commercial Officer at BioDelivery Sciences (BDSI) until it was acquired by Collegium Pharmaceutical in 2022. Under Mr. Plesha’s leadership, BDSI sales grew from $5 million to $160 million. He previously served as Senior Vice President of Gastrointestinal Sales at Salix Pharmaceuticals. During his fifteen-year tenure at Salix, Mr. Plesha led a nationwide salesforce that grew product sales to more than $1.5 billion annually. Before Salix, Mr. Plesha was a Regional Sales Manager for Oclassen Dermatologics, a division of Watson Laboratories, and in commercial roles of increasing responsibility at Solvay Pharmaceuticals. “I am excited to assume the leadership of Pelthos as we prepare to offer the first at-home therapy for the many patients who are completely untreated today or who need a more suitable option,” said Scott Plesha. “This is a company that has several meaningful milestones on the horizon and a team that is ready to execute to meet the needs of patients.” Ligand intends to commercialize ZELSUVMI in partnership with a capital provider and/or strategic partner. This is consistent with Ligand’s strategy to reposition and maximize the value of highly differentiated and promising pharmaceutical assets by combining premier management teams and outside funding sources in return for significant equity and royalty rights in the newly formed entities. To date, Ligand has created three companies utilizing this strategy: Viking Therapeutics, Primrose Bio, and OmniAb®. Pelthos is a wholly owned subsidiary of Ligand. About ZELSUVMI™ (berdazimer) topical gel, 10.3% ZELSUVMI (berdazimer) topical gel, 10.3% is a nitric oxide (NO) releasing agent indicated for the topical treatment of molluscum contagiosum in adults and pediatric patients one year of age and older. Complete prescribing information is available at . About Ligand Pharmaceuticals Ligand is a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Our business model seeks to generate value for stockholders by creating a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Our business model is based on funding programs in mid- to late-stage drug development in return for economic rights and licensing our technology to help partners discover and develop medicines. We partner with other pharmaceutical companies to attempt to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate our revenue. Our Captisol® platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. We have established multiple alliances, licenses and other business relationships with the world’s leading pharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Takeda, Gilead Sciences and Baxter International. For more information, please visit . Follow Ligand on X @Ligand_LGND. We use our investor relations website and X as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our website and our X account, in addition to following our press releases, SEC filings, public conference calls and webcasts. About Pelthos Therapeutics Pelthos Therapeutics is a biopharmaceutical company committed to commercializing innovative, safe, and efficacious therapeutic products to help patients with unmet treatment burdens. Our lead product ZELSUVMI™ (berdazimer) topical gel, 10.3%, for the treatment of molluscum contagiosum is now approved by the U.S. Food and Drug Administration. In addition to ZELSUVMI, Pelthos has a pipeline of potential product candidates that utilize our proprietary nitric oxide-based technology platform, NITRICIL™. More information is available at . Follow Pelthos on LinkedIn and X. Forward-Looking Statements This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. Words such as “plans,” “believes,” “expects,” “anticipates,” and “will,” and similar expressions, are intended to identify forward-looking statements. These forward-looking statements include: the timing of commercial launch of ZELSUVMI; the potential that ZELSUVMI could avoid surgical removal or more intensive therapies in some patients; and the possibility that Ligand’s strategy to maximize value through the creation of Pelthos Therapeutics will be successful. Actual events or results may differ from Ligand's expectations due to risks and uncertainties inherent in Ligand’s business, including, without limitation: the risk that Ligand and Pelthos may not commercially launch ZELSUVMI in late 2024 or at all; Ligand and Pelthos may not be able to successfully commercialize ZELSUVMI which will depend on a number of factors including coverage and reimbursement levels from governmental authorities and health insurers as well as market acceptance by healthcare providers; the market size for ZELSUVMI may be smaller than estimated; Ligand’s dependence on third parties in connection with product manufacturing and distribution of ZELSUVMI; Ligand may not be able to protect its intellectual property and patents covering ZELSUVMI which may be challenged or invalidated; and other risks described in Ligand’s prior press releases and filings with the Securities and Exchange Commission available at . Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this release. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. __________________________ 1 ZELSUVMI Package Insert. LNHC Inc. 2023.

JUPITER, Fla., March 28, 2024 (GLOBE NEWSWIRE) -- Dyadic International, Inc. (“Dyadic”, “we”, “us”, “our”, or the “Company”) (NASDAQ: DYAI), a biotechnology company focused on the efficient large-scale manufacture of proteins for use in human and animal vaccines and therapeutics and for use in non-pharmaceutical applications including food, nutrition, and wellness, today announced that Michael Tarnok is stepping down as Chairman of Dyadic’s board of directors (the “Board”) and that current member of the Board Patrick Lucy has been appointed to succeed him, in each case, effective immediately. Mr. Tarnok will continue to serve as a director through the end of his current term, which will end at the Company’s annual meeting in June 2025, at which time he expects to retire. In addition, Dr. Barry Buckland announced that he is retiring and therefore will not stand for re-election at the Company’s annual meeting in June 2024. The Board has decided not to fill the vacancy due to Dr. Buckland’s retirement which will result in a reduction of the size of the Board from seven to six members. Finally, Joseph Hazelton has been appointed Chief Operating Officer, effective immediately, and will oversee the day-to-day operations of the Company. Mr. Lucy joined the Board in January 2021 and serves on the company’s Science and Technology Committee. He is currently the President and Chief Executive Officer of RoslinCT US, a privately held cell therapy contract development and manufacturing organization based in Hopkinton, Massachusetts and Edinburgh, Scotland. Mr. Lucy has 33 years of experience in the biotechnology industry, including a founder of Pfenex Inc., a protein expression platform technology company that originated within The Dow Chemical Company (“Dow”). He was a member of the leadership team that led the commercial launch of the Pfenex Expression Technology™ platform in 2005 and participated in the spin out of the business from Dow in 2009 via a Series A venture financing. Throughout Pfenex’s history, Mr. Lucy led business/corporate development and portfolio strategy as Chief Business Officer and was a member of the team that successfully completed Pfenex’s initial public offering in 2014. During his tenure at Pfenex, Mr. Lucy completed over $1.5 billion dollars of partnership transactions, and Pfenex was ultimately acquired by Ligand Pharmaceuticals in October 2020 for up to $512 million. "I am excited to assume the role as Chairman of the Dyadic board of directors. On behalf of the entire Dyadic team, I would like to thank Mike Tarnok for his leadership as Chairman over the past ten years,” said Mr. Lucy. “I believe that Dyadic is poised to monetize the many scientific advances we have made with our C1 gene expression system, including the completion of the first Phase 1 clinical study in 2023, and our new Dapibus™ platform that is focused on producing high value proteins for food, nutrition, and wellness. I look forward to working with Mark Emalfarb, our CEO, and Joe Hazelton in his new role as Chief Operating Officer and the rest of our talented management team and Board with a laser focus on maximizing shareholder value.” Mark Emalfarb, Dyadic’s Chief Executive Officer commented, “Patrick has been an outstanding board member over the past three years and I am pleased that he has agreed to take on the role as Board Chairman at a pivotal time for Dyadic. We are accelerating commercialization of the C1 and Dapibus platforms for pharmaceutical and nonpharmaceutical applications. Under Michael Tarnok’s leadership, Dyadic has evolved from the industrial enzyme business and has developed a flexible, safe, and highly efficient platform for the development and production of biologics and we believe we are now poised to deliver impactful advancements that can potentially transform healthcare and food production. I could not be more pleased that Mike has agreed to complete his current term through June 2025, so we can continue to benefit from his expertise and guidance.” Mr. Emalfarb continued, “Barry has been an invaluable member of our Science and Technology Committee and has contributed greatly to the numerous scientific achievements we have accomplished over the last six years. We will miss him and wish him well in his future endeavors.” Mr. Emalfarb concluded, “Joe has been instrumental in refocusing the Company on core verticals with shorter-term revenue opportunities, playing a vital role in achieving strategic objectives. His promotion to Chief Operating Officer is well-deserved, and I'm confident he will further enhance Dyadic’s value by expanding the internal pipeline of high-value biologic products and accelerating the commercialization of assets like alpha-lactalbumin and recombinant human albumin.” “I am very excited to take on these additional responsibilities and have a more active role in overall corporate direction and execution of our strategic business plans to accelerate and exploit short-term revenue producing products and opportunities for pharmaceutical and non-pharmaceutical applications. I look forward to expanding our internal pipeline and improving our capability to develop more rapid custom solutions for collaborators and hastening the commercialization of current assets,” said Joe Hazelton, Dyadic’s new Chief Operating Officer. About Dyadic International, Inc. Dyadic International, Inc., is a biotechnology company focused on the efficient large-scale manufacture of proteins for use in human and animal vaccines and therapeutics and for use in non-pharmaceutical applications including food, nutrition, and wellness. Dyadic’s gene expression and protein production platforms are based on the highly productive and scalable fungus Thermothelomyces heterothallica (formerly Myceliophthora thermophila). Our lead platform, C1-cell protein production platform, is based on an industrially proven microorganism (named C1), which is currently used to speed development, lower production costs, and potentially improve performance of biologic vaccines and drugs at flexible commercial scales for the human and animal health markets. Dyadic has also developed the Dapibus™ filamentous fungal based microbial protein production platform to enable the rapid development and large-scale manufacture of low-cost proteins, metabolites, and other biologic products for use in non-pharmaceutical applications, such as food, nutrition, and wellness. Dyadic is focusing on leveraging its microbial platform technologies for itself and its collaborators in a wide range of applications, including human and animal vaccines, therapeutics, food, nutrition, wellness, and internal biological products. To learn more about Dyadic please visit http://www.dyadic.com. Safe Harbor Regarding Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, including those regarding Dyadic International’s expectations, intentions, strategies, and beliefs pertaining to future events or future financial performance, such as the outcomes of the personnel changes described herein, as well as the success of our protein production platforms. Forward-looking statements generally can be identified by use of the words “expect,” “should,” “intend,” “anticipate,” “will,” “project,” “may,” “might,” “potential,” or “continue” and other similar terms or variations of them or similar terminology. Forward-looking statements involve many risks, uncertainties or other factors beyond Dyadic’s control. These factors include, but are not limited to, the following: (i) our history of net losses; (ii) market and regulatory acceptance of our microbial protein production platforms and other technologies; (iii) competition, including from alternative technologies; (iv) the results of nonclinical studies and clinical trials; (v) our capital needs; (vi) changes in global economic and financial conditions; (vii) our reliance on information technology; (viii) our dependence on third parties; (ix) government regulations and environmental, social and governance issues; and (x) intellectual property risks. For a more complete description of the risks that could cause our actual results to differ from our current expectations, please see the section entitled “Risk Factors” in Dyadic’s annual reports on Form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission (“SEC”), as such factors may be updated from time to time in Dyadic’s periodic filings with the SEC, which are accessible on the SEC’s website and at www.dyadic.com. All forward-looking statements speak only as of the date made, and except as required by applicable law, Dyadic assumes no obligation to publicly update any such forward-looking statements for any reason after the date of this press release to conform these statements to actual results or to changes in our expectations. Contact:Dyadic International, Inc.Ping W. RawsonChief Financial OfficerPhone: (561) 743-8333Email: ir@dyadic.com