Ionis Pharmaceuticals (NasdaqGS:IONS) Q4 2025 Earnings call February 25, 2026 08:30 AM ET Speaker1Morning, welcome to Ionis's fourth quarter and full year 2025 financial results conference call. As a reminder, this call is being recorded. At this time, I'd like to turn the call over to Wade Walke, Senior Vice President of Investor Relations, to lead off the call. Please begin.Speaker3Thank you, Keith. Before we begin, I encourage everyone to go to the investors section of the Ionis website to view the press ...

Core Business and Business Model - Exegenesis Bio Inc. focuses on gene therapy and oligonucleotide drug development, established in 2019, with headquarters in the Cayman Islands and operational entities in Hangzhou and Guangzhou, China. The company utilizes two core technology platforms: AAVarta and SODA, targeting rare and common diseases for innovative therapy development [1] - The company has 11 candidate products in development, including treatments for spinal muscular atrophy (SMA), wet age-related macular degeneration (wAMD), and Fabry disease. The core product EXG001-307 (for SMA type 1) is in Phase III clinical trials, while EXG102-031 (for wAMD) and EXG202 (for retinal neovascular diseases) are in Phase I/II [1] Revenue and Financial Performance - As of the first nine months of 2025, the company reported revenue of 1.299 million RMB, primarily from R&D services for overseas clients, indicating a lack of commercialized products and a revenue scale significantly below industry averages [2][3] - The net loss for the first nine months of 2025 reached 94.33 million RMB, continuing a trend of increasing losses primarily due to high R&D expenditures, which accounted for 87.3% of total operating expenses [2] - The gross margin for the first nine months of 2025 was only 10%, reflecting a weak profitability of the current business model, which relies heavily on R&D services rather than product sales [2] Customer and Supplier Concentration - The company’s revenue is entirely dependent on a single overseas client, resulting in a customer concentration of 100%, which poses a significant risk to business continuity [3][7] - The company has a high dependency on suppliers, with the top five suppliers accounting for 47.6% of procurement in the first nine months of 2025, indicating potential supply chain risks [8] Financial Challenges - As of September 2025, the company faced severe financial challenges, with net current liabilities of 1.632 billion RMB and a cash burn rate of approximately 70 million RMB per month, suggesting that existing cash reserves can only sustain operations for about 3.7 months [5][6] Competitive Landscape - Compared to peers, Exegenesis Bio's R&D efficiency is lower, with 145 million RMB spent in 2024 to advance only one Phase III and two Phase I/II products, while competitors have achieved more significant milestones with higher investments [6] - In the SMA treatment market, competition is intense, with Novartis's Zolgensma already approved globally, and domestic competitors advancing more rapidly in clinical trials [6][10] Management and Governance - The company is controlled by a founding team holding 31.16% of voting rights, which may lead to a lack of checks and balances in decision-making due to concentrated ownership [9] - The management team has extensive experience in gene therapy, but there is a lack of transparency regarding their compensation and incentive mechanisms [9] Regulatory and Commercialization Risks - The company faces multiple risks related to clinical development, regulatory approval, and commercialization, particularly with the core product's clinical data showing inferior efficacy compared to competitors [10][11][12] - As a biotechnology company under Chapter 18A, it must meet ongoing R&D requirements post-listing, with potential delisting risks if core product development fails [11] - The company has not yet established a sales team, raising concerns about its commercialization capabilities in a competitive market [12]

Company Overview - REGENXBIO is experiencing a transformational year, having a legacy of approximately 15 years in AAV gene therapy, initially focusing on out-licensing products like Zolgensma derived from its original intellectual property and technology [2] - In the last 8 to 10 years, the company has shifted towards developing new programs internally [2] Technology and Development - The company utilizes NAV technology, which includes over 100 vectors within the NAV family, and has five licensees primarily using AAV8 and AAV9 [3] - REGENXBIO has dosed over 5,000 patients with its technology over the years, indicating a significant level of experience and application in the field [3]

Summary of Regenxbio FY Conference Call (January 14, 2026) Company Overview - **Company**: Regenxbio (NasdaqGS: RGNX) - **Key Speakers**: Curran Simpson (CEO), Mitch Chan (CFO), Dr. Steve Pakola (CMO) [1] Industry and Technology - **Industry**: Gene Therapy - **Technology**: AAV (Adeno-Associated Virus) gene therapy with over 5,000 patients dosed [2][3] - **Focus**: Development of new capsids to enhance therapeutic efficacy and safety [5] Core Points and Arguments Pipeline and Product Development - **BLA Review**: The company has a Biologics License Application (BLA) under review for the Hunter program, with a PDUFA date of February 8, 2026 [8][22]. - **Late-Stage Programs**: Top-line readouts expected for two late-stage programs: Duchenne program (RGX-202) in Q2 2026 and wet AMD program (RGX-314) with AbbVie later in 2026 [4][8]. - **Duchenne Program**: Aiming to provide functional benefits to children with Duchenne muscular dystrophy, with pivotal data showing significant improvements in patient outcomes [10][11][19]. - **Wet AMD Program**: RGX-314 is positioned as a potential first non-rare gene therapy approved, with significant commercial readiness efforts in collaboration with AbbVie [9][25]. Manufacturing and Scalability - **Manufacturing Capabilities**: The company has advanced manufacturing processes, capable of producing 2,500 doses per year for RGX-202 and up to 350,000 doses for RGX-314 [28][29]. - **Quality Control**: Achieved an 80% full capsid level in batches, which is critical for safety and efficacy [29]. Safety and Efficacy - **Immune Suppression Regimen**: A proactive immune suppression strategy has been implemented to enhance safety and efficacy, allowing for higher dosing without significant adverse effects [36][37]. - **Clinical Outcomes**: Positive safety profiles and functional benefits observed in patients, with significant improvements in NSAA scores [19][17]. Additional Important Content - **Global Expansion**: Plans for expanding clinical studies outside the U.S. to address broader patient needs [21][39]. - **Partnerships**: Collaboration with AbbVie for the wet AMD program, leveraging their existing sales force and expertise in ophthalmology [43][44]. - **Market Potential**: The company is targeting significant unmet needs in rare diseases and chronic retinal diseases, with a focus on long-term patient outcomes and reducing treatment burdens [31][27]. Conclusion - **Future Outlook**: Regenxbio is positioned for a transformative year with multiple late-stage catalysts, a strong manufacturing base, and a commitment to patient-centric outcomes in gene therapy [31].

Core Insights - The high pricing of gene therapies, such as Novartis' Itvisma at $2.59 million, reflects the substantial R&D and production costs associated with these treatments [1][2][3] - The gene therapy market is projected to grow significantly, with an estimated market size of $9.03 billion in 2024, expected to reach $64.64 billion by 2033, representing a compound annual growth rate of 27.6% [7] Pricing and Market Dynamics - Gene therapies are characterized by high costs due to complex R&D processes, with an average clinical trial cost of $1.943 billion [3] - The pricing of gene therapies in the global market typically exceeds $2 million, with some therapies like Lenmeldy priced at $4.25 million [2] - In contrast, the Chinese market offers lower-priced gene therapies, such as the domestically approved 波哌达可基注射液 at approximately ¥93,000 per bottle, but still results in high treatment costs for patients [2] R&D Challenges and Innovations - The lengthy R&D cycle, often exceeding 10 years, and stringent quality control standards contribute to the high costs of gene therapies [3][4] - Innovations in delivery systems and gene editing tools are essential for reducing costs and improving the efficacy and safety of gene therapies [6][8] Commercialization and Accessibility - The high costs of gene therapies create significant barriers to patient accessibility, despite their potential for long-term efficacy [4] - Strategies such as commercial insurance coverage, pay-for-performance models, and installment payment options are critical for improving patient access to these therapies [6] Investment Trends and Market Opportunities - The gene therapy sector continues to attract investment, with approximately 41 financing events in 2024, totaling over ¥2.5 billion [8][9] - There is a growing interest in companies with foundational technology platforms, particularly in new delivery systems and precision editing tools, as investors seek differentiation in the market [9]

Financial Data and Key Metrics Changes - The company reported a significant milestone with the successful readout of its phase III trial in October 2024, marking it as the first muscle-targeted treatment for SMA [2][5] - The company has a cash balance of $369 million, which is expected to sustain operations into 2027 [54] Business Line Data and Key Metrics Changes - The primary asset, apitegromab, is positioned to serve patients globally with SMA, with plans for clinical development programs for additional myostatin inhibitors [5][21] - The phase III trial demonstrated a statistically significant improvement in motor function for patients receiving apitegromab alongside SMN-targeted therapies, with a p-value of 0.01 [18] Market Data and Key Metrics Changes - In the U.S., approximately 7,000 patients have received at least one SMN-targeted treatment, with a global total of about 35,000 patients [20] - The combined annual revenue from existing SMN-targeted therapies is approximately $5 billion, indicating a robust market for SMA treatments [21] Company Strategy and Development Direction - The company aims to build a global biotech powerhouse, focusing on rare neuromuscular diseases, starting with SMA and expanding into other indications [3][5] - Plans include a methodical expansion into Europe, Asia-Pacific, and Latin America, targeting a 50-country operating platform [5][32] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the unique approach to myostatin inhibition, which differentiates the company from competitors focusing solely on motor neuron survival [12][24] - The company anticipates a resubmission of its BLA and a potential launch in the U.S. in 2026, following a constructive meeting with the FDA [47][52] Other Important Information - The company is currently addressing manufacturing issues that led to a Complete Response Letter (CRL) from the FDA, with a focus on remediation plans at its drug product manufacturer [41][44] - The company is also advancing its pipeline with SRK-439, a next-generation myostatin inhibitor, expected to enter clinical trials soon [48][50] Q&A Session Summary Question: What is the state of FDA interactions post-CRL? - The company received a CRL due to manufacturing issues at its drug product manufacturer, but management remains optimistic about resolving these issues and expects to resubmit and launch in 2026 [41][47] Question: How does the company plan to execute its commercial strategy? - The company plans to leverage its experience in rare diseases to identify and treat patients already diagnosed with SMA, ensuring a smooth market entry for apitegromab [26][28]

Financial Data and Key Metrics Changes - The company reported a significant transformation over the past 12 to 14 months, particularly following the positive readout of its phase III trial in October 2024, marking it as the first muscle-targeted treatment for SMA [2][5] - The company has a cash balance of $369 million, which is expected to sustain operations into 2027, with plans to expand its loan facility to support the upcoming launch [50] Business Line Data and Key Metrics Changes - The primary asset, apitegromab, is positioned as a muscle-targeted treatment for SMA, with clinical trials demonstrating statistically significant improvements in motor function when used alongside existing SMN-targeted therapies [16][20] - The company anticipates a multi-billion dollar opportunity for apitegromab, estimating over $2 billion in annual revenue from SMA alone [21] Market Data and Key Metrics Changes - In the U.S., approximately 7,000 patients have received at least one SMN-targeted treatment, with a global total of about 35,000 patients [19] - The existing SMN-targeted therapies generate approximately $5 billion in annual revenues, indicating a robust market for SMA treatments [20] Company Strategy and Development Direction - The company aims to build a global operating platform across 50 countries, focusing on expanding its reach in Europe, Asia-Pacific, and Latin America [5] - Future plans include entering clinical trials for other rare neuromuscular disorders, with indications such as FSHD and DMD being assessed [30] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in overcoming the recent CRL issued by the FDA, emphasizing that the remaining issue is solvable and that approval is a matter of when, not if [48][49] - The company is committed to a collaborative approach with the FDA and its manufacturing partners to expedite the approval process for apitegromab [42] Other Important Information - The company has established a world-class executive team to drive its strategic vision, with leadership experienced in building successful biotech companies [3][4] - The company is also developing SRK-439, a next-generation myostatin inhibitor, which is expected to enhance its rare neuromuscular franchise [45][46] Q&A Session Summary Question: What is the state of FDA interactions post-CRL? - The company received a CRL due to manufacturing issues at its drug product manufacturer, but management remains optimistic about resolving these issues and expects to resubmit and launch in 2026 [32][44] Question: How does the company plan to execute its commercial strategy? - The company plans to leverage its existing knowledge of the rare disease market, focusing on patients already diagnosed and receiving treatment, to effectively launch apitegromab [26][27]

Core Viewpoint - The article discusses the rising trend of high-priced gene therapies, particularly focusing on Novartis's newly approved gene therapy Itvisma for spinal muscular atrophy, priced at $2.59 million, which highlights the challenges of commercialization and reimbursement in the gene therapy market [3][6]. Pricing and Market Dynamics - Novartis's Itvisma is priced at $2.59 million, surpassing its earlier product Zolgensma, which was priced at $2.125 million [3][4]. - The global list of the most expensive drugs includes several gene therapies, with the top position held by Kyowa Kirin's Lenmeldy at $4.25 million, followed by CSL's Hemgenix at $3.5 million [4][5]. - The article notes that despite the high prices, many gene therapies face commercialization challenges, as seen with Bluebird Bio's products, which have not achieved significant sales despite their high price tags [5][6]. Sales Performance and Market Challenges - Zolgensma generated $1.2 billion in sales in 2024, maintaining its performance from the previous year, while Bluebird Bio's Lyfgenia only achieved $10 million in sales in Q3 2024 [6][7]. - The article emphasizes the disparity between the high prices of gene therapies and their actual market performance, indicating a potential "value without market" scenario [5][6]. Future Outlook and Market Growth - The global gene therapy market is projected to grow from $9 billion in 2024 to $11.5 billion in 2025, with an expected compound annual growth rate of 27.6% [7]. - The article suggests that a balance between innovation and accessibility is crucial for the future of gene therapies, with a collaborative approach needed from payers, regulators, and pharmaceutical companies [7][8].

Core Viewpoint - A rare disease gene therapy, Itvisma, developed by Novartis, has gained attention for its high price of $2.59 million, aimed at treating spinal muscular atrophy (SMA) in patients aged two and above with a specific genetic mutation [1][4]. Pricing and Market Position - Itvisma's price of $2.59 million exceeds that of Novartis's earlier product, Zolgensma, which was priced at $2.125 million and is now only available for children under two [1]. - Despite its high price, Itvisma barely ranks among the top ten most expensive drugs globally, as reported by Fierce Pharma [1]. - The most expensive drug as of 2025 is Lenmeldy, priced at $4.25 million, followed by Hemgenix at $3.5 million, and other gene therapies priced above $3 million [2][3]. Market Dynamics and Challenges - The gene therapy market is transitioning from concept validation to large-scale commercialization, facing challenges such as high prices, market promotion difficulties, and insurance reimbursement issues [3][4]. - Companies like Bluebird Bio, despite having multiple gene therapies approved, struggle with commercialization, as evidenced by low sales figures for their high-priced therapies [3][4]. Sales Performance - Zolgensma has shown relatively successful commercialization, with sales of $1.2 billion in 2024, maintaining the same level as the previous year [4]. - In contrast, Bluebird Bio's therapies, despite their high prices, reported only $10 million in sales for one product in Q3 2024 [3]. Future Outlook - The global gene therapy market is projected to grow from $9 billion in 2024 to $11.5 billion in 2025, with an expected compound annual growth rate of 27.6% [5]. - Novartis claims that Itvisma's one-time treatment is 35% to 46% cheaper over a ten-year span compared to existing long-term therapies [5].

Core Viewpoint - The approval of Itvisma by Novartis marks a significant advancement in gene therapy for spinal muscular atrophy (SMA), with a wholesale price of $2.59 million, highlighting the growing market for high-cost life-saving drugs and the potential for gene therapy to become a mainstream treatment option [4][5][10]. Gene Therapy Market Dynamics - The global gene therapy market is at a pivotal point, expected to grow at an annual rate of over 20% in the next 5-10 years, driven by technological advancements, clearer regulatory pathways, and innovative payment models [5][12]. - Itvisma is the first gene therapy approved for a broader patient demographic with SMA, emphasizing its rarity and the high barriers to entry in the market due to substantial R&D investments [5][8]. Pricing Strategy and Market Comparison - Novartis' pricing strategy for Itvisma is informed by the $9.4 billion total R&D investment for Zolgensma, which was previously priced at $2.1 million [7][8]. - The pricing of Itvisma and Zolgensma significantly exceeds estimates from industry observers, indicating a disconnect between market expectations and pharmaceutical pricing strategies [7][8]. Clinical Efficacy and Safety - Itvisma's approval is based on robust clinical trial data demonstrating significant improvements in motor function for SMA patients, with a favorable safety profile [9][10]. - The treatment offers a one-time administration approach, reducing the burden of ongoing therapies that are common with existing SMA treatments [9][10]. Competitive Landscape - Itvisma competes directly with Spinraza, the first approved SMA treatment, which has undergone significant price reductions in markets like China after being included in insurance coverage [10][11]. - The gene therapy market is witnessing increased competition as more companies invest in gene editing and delivery systems, necessitating continuous innovation and differentiation [5][12]. Future Growth and Investment Trends - The gene therapy market is projected to reach $64.64 billion by 2033, with a compound annual growth rate of 27.6% from 2024 to 2033, driven by technological breakthroughs and accelerated regulatory approvals [12][13]. - Major pharmaceutical companies are actively acquiring biotech firms to enhance their gene therapy portfolios, indicating strong investor interest and market potential [13][14]. Challenges Ahead - Despite the promising outlook, gene therapy faces challenges such as high production costs, short shelf life of viral vectors, and the need for a balance between innovation incentives and drug accessibility [16][17]. - The industry is also grappling with the complexities of developing therapies for common diseases, where competition is fierce and clinical efficacy must be convincingly demonstrated [14][16].