Core Insights - The small nucleic acid drug sector is experiencing a significant surge, marking the beginning of a golden era driven by technological breakthroughs and capital enthusiasm [2][11][22] Industry Developments - On January 5, 2026, Sanofi's APOC3 siRNA drug Plozasiran was approved for domestic market use to treat hyperlipidemia [1] - On January 9, 2026, Rebio Biotech, known as "China's first small nucleic acid stock," successfully listed on the Hong Kong Stock Exchange, with its stock price soaring by 40% on the first day, leading to a market capitalization exceeding 13 billion HKD [1] - China National Pharmaceutical Group announced a 1.2 billion CNY acquisition of Hegia Biotech, securing the world's first clinically validated liver-targeted delivery platform capable of annual dosing [1] Market Trends - The global small nucleic acid drug market has seen nearly 100 business development (BD) collaborations in the past three years, with transaction numbers and amounts increasing annually, reaching over 30 BD deals in 2025 totaling nearly 30 billion USD [4][9] - Notable transactions in 2025 included Novartis acquiring Avidity Biosciences for 12 billion USD and multiple other significant deals involving RNA therapies [7][9] Clinical Advancements - Ionis's APOC3 ASO drug Olezarsen showed promising results in reducing triglyceride levels by up to 72% in patients with severe hypertriglyceridemia, leading to an increase in peak annual sales forecast from 1.5 billion USD to 2.5 billion USD [12] - GSK's ASO therapy Bepirovirsen is expected to be the first drug to achieve functional cure for chronic hepatitis B, with a peak annual sales potential of 2 billion USD [12] Emerging Opportunities - The small nucleic acid drugs are expanding into various therapeutic areas, including obesity and kidney diseases, with promising results from clinical trials demonstrating significant weight loss and metabolic health improvements [13][15] - The number of small nucleic acid drugs in development globally has surpassed 1,200, with siRNA and ASO therapies being the most prominent [17] Strategic Collaborations - Domestic companies are increasingly recognized for their innovative value in small nucleic acid drugs, with active BD transactions, including significant collaborations by Rebio Biotech and other firms [18][21] - Companies like Saintin Biotech are forming strategic partnerships with major pharmaceutical firms to advance their small nucleic acid drug pipelines [19] Conclusion - The convergence of technological advancements, capital influx, and successful clinical outcomes is propelling small nucleic acid drugs into a pivotal position within the pharmaceutical industry, with China poised to become a global innovation hub [22]

Key Takeaways IONS shares rose 2.5% after the European Commission approved Dawnzera to prevent recurrent HAE attacks.Ionis partnered with Otsuka ex-U.S., & is eligible for a $15M milestone payment with approval in the EU.Dawnzera cut mean monthly HAE attacks by 94% at one year in the OASISplus study.Ionis (IONS) and its Japanese partner, Otsuka Pharmaceutical, announced that the European Commission has approved Dawnzera (donidalorsen) for the prevention of recurrent attacks of hereditary angioedema (HAE) in ...

This is my lucky 13th article on Ionis ( IONS ), following my 09/2025 article — "Ionis: Recent Approvals, Upcoming Catalysts To Spur Strong Upside (Rating Upgrade)". It has been thumbs up for Ionis since this lastWriting under the pseudonym "out of ignorance", I very much regard investing as a learning process. Investing failures are tuition paid. Investing successes enter the trove of lessons learned. In my Seeking Alpha articles I share my experience from decades of investing and from ~5 years of focused ...

Core Insights - The small nucleic acid drug sector in China is entering a "capital year" in 2026, with increasing market interest and significant transactions, such as the successful IPO of Rebio and the acquisition of Hegia Biotech by China National Pharmaceutical Group for 1.2 billion yuan [1] - The global small nucleic acid drug market is characterized by a "three strong" dominance, with Alnylam, Ionis, and Sarepta leading the industry due to their technological barriers and commercialization advantages [1][5] - The market for small nucleic acid drugs is projected to grow from $5.247 billion in 2024 to $46.7 billion by 2033, with a compound annual growth rate (CAGR) of 25% [10] Market Dynamics - In 2024, global sales of small nucleic acid drugs reached $5.247 billion, with Ionis and Biogen's Spinraza leading at $1.573 billion, followed by Alnylam's Amvuttra at $0.971 billion and Sarepta's DMD treatments at $0.967 billion [2] - The current landscape features two main technological routes: Antisense Oligonucleotides (ASO) and small interfering RNA (siRNA), each with distinct mechanisms and advantages [4][7] - Alnylam has established itself as a leader in RNAi therapy, with a high clinical conversion rate of 64.3%, significantly above the industry average of 5.7% [7] Competitive Landscape - Ionis focuses on ASO technology, having launched the first ASO drug in 1998 and currently holding nine of the twelve approved ASO drugs globally, including the top-selling Spinraza [7][8] - Sarepta has specialized in muscle diseases, particularly DMD, with four approved drugs and a revenue growth of over 50% in 2024, reaching $1.9 billion [9] - The competitive landscape is evolving, with multinational corporations (MNCs) increasingly entering the market through acquisitions and collaborations, reflecting a growing interest in the sector [16][19] Emerging Opportunities - The market is entering a commercialization phase, with potential blockbuster products needed to transition from niche to mainstream [10] - Alnylam's Amvuttra and Novartis's Leqvio are identified as strong candidates for future blockbuster status, with Amvuttra projected to exceed $2 billion in sales by 2025 [12][13] - New products like Arrowhead's Plozasiran and Alnylam's Zilebesiran are expected to broaden the treatment landscape, moving from rare diseases to more common conditions [15] Strategic Movements - MNCs are actively pursuing partnerships and acquisitions to enhance their presence in the small nucleic acid space, with notable transactions in 2025 exceeding $36.473 billion [16][18] - Companies like Novartis are building comprehensive pipelines across various therapeutic areas, including cardiovascular and rare diseases, to strengthen their competitive position [18] - Chinese biotech firms are emerging as significant players, leveraging unique delivery technologies and cost advantages, leading to increased collaborations with MNCs [19][20]

PresentationGreat. Good morning, everyone. Welcome. My name is Jess Fye, large-cap biotech analyst at JPMorgan, and we're continuing the 44th Annual Healthcare Conference this morning with Ionis. You're going to hear a presentation from the management team, and then we're going to go into some Q&A. So if you have any questions in the room, just raise your hands, and someone will bring you a microphone or you can submit them online, and I can read them off the iPad up here. So with that out of the way, let m ...

Summary of Ionis Pharmaceuticals FY Conference Call Company Overview - **Company**: Ionis Pharmaceuticals (NasdaqGS:IONS) - **CEO**: Brett Monia - **Conference Date**: January 13, 2026 Key Industry Insights - Ionis has transitioned from an R&D organization to a fully integrated commercial biotechnology company, achieving its first two independent commercial launches in 2025: **Tringulza** and **Donzera** [4][5] - The company has a robust pipeline with **11 medicines in phase 3 development**, indicating a strong future for product approvals and revenue growth [6] Core Products and Launches - **Tringulza**: Approved for familial chylomicronemia syndrome (FCS), generating **$105 million** in net U.S. product sales in 2025 [13] - **Donzera**: Approved for hereditary angioedema (HAE) prophylaxis, launched in September 2025, with positive early prescription trends [8][9] - **Olezarsen**: Positioned as a new standard of care for severe hypertriglyceridemia (SHTG), with a peak revenue potential now upgraded to **over $2 billion** [17][35] Clinical Achievements - Six positive phase 3 data readouts leading to four approved medicines: Tringulza, Donzera, Wainua, and Qalsody [6] - Olezarsen demonstrated a **72% reduction** in fasting triglycerides and an **85% reduction** in acute pancreatitis event rates at 12 months [15][16] - Zolexarsen for Alexander disease shows unprecedented disease-modifying impact, with plans for NDA submission and launch in the second half of 2026 [21][24] Financial Projections - Anticipated **$4 billion** in potential annual peak product revenue from wholly owned pipeline and **$2 billion** from partner medicines, totaling **over $6 billion** at peak [26] - Expected to achieve cash flow break-even by **2028** with sustained positive cash flow thereafter [26] Market Strategy and Launch Preparations - The launch strategy for Olezarsen in SHTG is based on strong physician enthusiasm and a high unmet need, with a field team of **200 individuals** already hired and trained [33][31] - Pricing strategy for Olezarsen is projected between **$10,000 to $20,000** in the U.S., with ongoing engagement with payers to ensure access [37][38] Risks and Challenges - New product launches inherently carry uncertainty, but the demand for Olezarsen is expected to be strong due to the inadequacy of current treatments for SHTG [36] - The company is preparing for potential challenges in achieving broad access and acceptance among healthcare providers [37] Future Outlook - Ionis is well-positioned for continued growth with a steady cadence of new medicines expected to reach the market, including Olezarsen and Zolexarsen in 2026 [24][25] - The company aims to leverage its strong pipeline and market presence to drive revenue growth and enhance shareholder value [28]

44th Annual J.P. Morgan Healthcare Conference 2026 Breakthrough Therapies Driving Accelerating Growth Brett Monia, Ph.D. Chief Executive Officer January 2026 | Nasdaq: IONS Forward-Looking Statements This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement desc ...

Exhibit 99.1 Ionis well-positioned for continued momentum and substantial value creation in 2026 with two new independent launches and several pivotal data readouts CARLSBAD, Calif., January 12 – Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced highlights from the Company's 2025 achievements and provided additional updates on key milestones expected in 2026. Ionis will provide a business update at the 44th Annual J.P. Morgan Healthcare Conference on Tuesday, January 13 at 8:15am PT; the presentati ...

Core Viewpoint - The article discusses the revolutionary shift in small nucleic acid drugs, highlighting their potential to transition from symptomatic treatment to addressing root causes, marking a significant advancement in the pharmaceutical industry [4]. Group 1: Small Nucleic Acid Drug Technology - Small nucleic acid drugs (siRNA, ASO, etc.) are considered the "third wave" of drug development, following small molecules and antibody drugs [4]. - These drugs are not limited by their molecular structure and can target a broader range of disease pathways, significantly increasing the probability of successful drug development [4]. - Current advancements in delivery technologies and chemical modifications have led to extended half-lives for these drugs, improving patient compliance in chronic disease management [4]. Group 2: Market Growth and Commercialization - The global small nucleic acid drug market is projected to reach $20.6 billion by 2029 and $54.9 billion by 2034, with a compound annual growth rate (CAGR) of 21.6% [5]. - Major players like Alnylam, Ionis, and Arrowhead are leading the market, with multinational corporations (MNCs) such as Novartis and Roche investing heavily in this sector [5]. - Alnylam's core product, Amvuttra, is expected to exceed $2 billion in sales by 2025, indicating strong market performance [6]. Group 3: Technological Breakthroughs - Arrowhead has developed RNAi therapies targeting various diseases through its TRiM platform, expanding the application of small nucleic acid drugs beyond liver diseases [7]. - Avidity Biosciences has made significant progress in muscle tissue delivery using antibody-oligonucleotide conjugates (AOC) technology, indicating a broader therapeutic potential [7]. Group 4: China's Small Nucleic Acid Drug Industry - The Chinese small nucleic acid drug industry is experiencing a qualitative leap, overcoming delivery patent barriers and demonstrating global competitiveness in target selection and molecular design [8]. - A complete industrial chain has emerged in China, with domestic raw materials achieving localization, thus reducing R&D costs [8]. - Significant business development (BD) transactions have occurred, including a record $5 billion deal between Wobang Pharmaceutical and Novartis, showcasing the global recognition of Chinese innovation [8].

Core Insights - GSK shared data from two pivotal Phase 3 studies, B-Well 1 and B-Well 2, for bepirovirsen, an investigational treatment for chronic hepatitis B, involving over 1,800 patients [1] - The studies met their primary endpoint, showing a statistically significant and clinically meaningful functional cure rate for bepirovirsen compared to standard care alone [3] - If approved, bepirovirsen could become the first finite, six-month therapeutic option for chronic hepatitis B [5] Financial and Partnership Details - Ionis received an upfront payment, license fee, and development milestone payments from GSK, with potential additional payments of $150 million and tiered royalties of 10-12% on net sales of bepirovirsen [2] - The collaboration between Ionis and GSK began in 2019 when GSK licensed bepirovirsen from Ionis [1] Study Results and Future Plans - The B-Well studies demonstrated an acceptable safety and tolerability profile consistent with previous studies, with full results to be presented at a scientific congress and submitted for regulatory approvals in early 2026 [4] - The studies showed significantly higher functional cure rates in patients with baseline surface antigen levels ≤1000 IU/ml [3] Analyst Commentary - Analysts from William Blair noted that Ionis is well-positioned with five Phase 3 readouts expected in 2026, highlighting bepirovirsen as an underappreciated opportunity in the market [6] - The performance of Gilead Science's Vemlidy, projected to exceed $1 billion in revenue for fiscal 2025, suggests a growing market for hepatitis B treatments [6] Market Reaction - Following the announcement, Ionis Pharmaceuticals shares increased by 4.06% to $84.80, while GSK shares rose by 1.20% to $51.16 [8]