PresentationMavic Cuevas Good morning and good afternoon. Welcome to our 12th Annual Social Impact and Sustainability Event. Before we start, I would like to quickly read our safe harbor statement. The information presented today contains forward-looking statements that involve known and unknown risks, uncertainties and other factors. These may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. For a description of so ...

Summary of Novartis Conference Call Company Overview - **Company**: Novartis - **Focus**: Transitioned from a diversified healthcare conglomerate to a pure-play innovative medicines company, emphasizing four core therapeutic areas and advanced technology platforms [3][4][5] Key Industry Insights - **Global Health Pipeline**: Novartis is committed to addressing neglected diseases, particularly malaria, with a focus on drug discovery, development, and delivery [8][9][10] - **Malaria Focus**: The company is developing new antimalarial treatments to combat rising resistance and improve patient outcomes, including a new formulation for infants [12][13][18][25] Core Strategic Priorities 1. **Global Health Innovation**: Aiming to find breakthroughs for neglected diseases and ensure access to innovative medicines in low and middle-income countries [4][5][6] 2. **Inclusion and Access**: Addressing healthcare disparities by embedding access principles across research, development, and commercialization [5][46] 3. **Environmental Sustainability**: Committed to reducing the environmental footprint and achieving net zero emissions by 2040 [52][53] Financial and Operational Highlights - **Clinical Trials**: Currently running 11 clinical trials across 14 low and middle-income countries, focusing on diseases with significant unmet needs [12] - **Investment in R&D**: Over $200 million invested in environmental sustainability initiatives, yielding measurable financial benefits [68][69] Social Impact and Sustainability - **Inclusive Health Accelerators**: Designed to reach underserved populations in priority markets, focusing on specific therapeutic areas like prostate cancer and cardiovascular disease [46][47] - **Partnerships**: Collaborations with organizations like Medicines for Malaria Venture to enhance global health outcomes and drive innovation [19][32] Challenges and Future Outlook - **Public Funding Constraints**: Noted reductions in official development assistance impacting health systems, but Novartis' self-sustainable programs remain unaffected [73][74] - **Innovation in Malaria Treatment**: The development of Ganaplacide-Lumefantrine is seen as a significant advancement in the fight against malaria, with potential for high barriers to resistance [35][36][38] Recognition and Achievements - **Access to Medicines Index**: Novartis has been recognized as a leader in the Access to Medicines Index for the past 10 years, achieving the number one position this year [60] - **Sustainability Ratings**: Achieved AAA rating from MSCI and improved controversy scores, reflecting strong commitment to social impact and sustainability [60] Conclusion - Novartis is focused on delivering innovative medicines while addressing global health challenges, enhancing access, and committing to sustainability, positioning itself as a leader in the pharmaceutical industry [61][62]

Summary of Novartis Update / Briefing December 01, 2025 Company Overview - **Company**: Novartis (NYSE:NVS) - **Industry**: Pharmaceuticals, specifically focusing on malaria treatment and global health initiatives Key Points and Arguments Malaria Treatment Innovations - Novartis is committed to developing new medicines to combat malaria, emphasizing the need for innovation in pharmaceuticals to stay ahead of the malaria parasite's resistance [1][4] - The company has a partnership with Medicines for Malaria Venture (MMV) that has lasted for 20 years, focusing on delivering new medicines and formulations [3] - Recent clinical trial data for the ganaplacide-lumefantrine combination shows promising efficacy and a high barrier to resistance, marking a significant advancement in malaria treatment [5][6] - The ganaplacide-lumefantrine combination is expected to have transmission-blocking properties, which could be game-changing in the fight against malaria [6][7] Future of Malaria Innovation - There is optimism about entering a new age of malaria innovation, focusing not only on treatment but also on prevention and eventual elimination of the disease [9][10] - New technologies being explored include long-acting injectables and single-dose cures, which could significantly improve treatment accessibility and effectiveness [11][10] Social Impact and Sustainability Strategy - Novartis is enhancing its social impact and sustainability strategy through inclusive health accelerators aimed at reaching underserved populations in priority markets [15][18] - The company recognizes that disparities in healthcare access are driven by socioeconomic conditions, geography, and healthcare system capacity [16] - Initiatives are being launched in the U.S. focusing on prostate cancer, cardiovascular disease, and breast cancer, with a phased approach starting in 2026 [19] Addressing Health Disparities - The inclusive health accelerators aim to identify and address barriers to care for underserved populations, particularly in low-income areas [18][20] - Specific strategies include community-based education, navigation support for patients, and training for healthcare providers [21] Environmental Sustainability Efforts - Novartis has updated its environmental sustainability framework, focusing on climate and nature, with a goal to achieve net zero emissions by 2040 [24][25] - The company has made significant progress towards its 2025 targets, including a 90% reduction in scope one and two emissions by 2030 [25][26] Financial and Operational Resilience - Novartis has invested over $200 million in environmental sustainability efforts, which have resulted in measurable financial benefits through reduced energy consumption and waste [40][41] - The company is also focusing on supply chain resilience, with a recent $23 billion investment in new manufacturing facilities in the U.S. to ensure uninterrupted supply of medications [45][46] Future Outlook - Novartis is on track to meet its current social impact targets and is working on new targets to be announced in early 2026, which will continue to focus on access to medicines and climate-related commitments [51] Additional Important Content - The partnership with MMV has been crucial in developing new malaria treatments, highlighting the importance of collaboration in pharmaceutical innovation [3][4] - The discussion around the financial rationale for global health programs emphasizes that societal impact is the primary motive, with financial sustainability being a secondary consideration [36] - The company is committed to addressing the impact of climate change on health, recognizing the need for a climate-resistant pipeline [22][23] This summary encapsulates the key insights from the Novartis briefing, focusing on their commitment to malaria treatment innovation, social impact initiatives, and sustainability efforts.

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].

Investment Rating - The report indicates a positive investment outlook for the oral FXIa inhibitor asundexian, particularly following its successful Phase III trial results for preventing recurrent strokes [21][25]. Core Insights - The oral FXIa inhibitor asundexian has shown significant efficacy in reducing the risk of ischemic stroke in patients with non-cardioembolic ischemic stroke or high-risk transient ischemic attack, achieving its primary efficacy and safety endpoints in the OCEANIC-STROKE study [21][25]. - The report highlights the potential of FXI inhibitors to provide safer anticoagulation options with lower bleeding risks compared to traditional anticoagulants [9][10]. - The report discusses the diverse potential indications for FXI/XIa inhibitors, including prevention of venous thromboembolism (VTE) in orthopedic surgeries, stroke prevention in atrial fibrillation patients, and treatment of cancer-associated VTE [13][10]. Summary by Sections Section 1: Focus on Innovative Drugs - The report reviews the recent advancements in innovative drugs, particularly in the anticoagulant space, emphasizing the role of FXI inhibitors [4][5]. Section 2: Mechanism of Action - FXIa plays a crucial role in pathological thrombus formation while having a limited role in hemostasis, making it an ideal target for developing safer anticoagulants [9][10]. Section 3: Clinical Development Progress - Asundexian has successfully completed Phase III trials, while other FXIa inhibitors like milvexian have faced challenges, including trial terminations due to efficacy concerns [30][33]. - The report details the ongoing clinical trials for various FXI inhibitors, including those by companies like Bayer, BMS, and Regeneron, highlighting their respective stages of development and potential applications [20][39][45]. Section 4: Market Potential - The report underscores the significant market potential for FXI inhibitors, given the high incidence of stroke and VTE, with approximately 12 million people affected by stroke annually worldwide [25][21].

Group 1 - Novartis AG is recognized as a strong slow growth stock, with a projected sales CAGR of 6% from 2024 to 2029, supported by recent meetings with TD Cowen [1][2] - Key growth contributors include existing medicines such as Cosentyx, Pluvicto, Kisqali, Leqvio, Kesimpta, and Scemblix, which are expected to mitigate the impact of generic erosion, particularly for Entresto [2] - The company has a robust position in immunology with products like Rhapsido and ianalumab, which are considered "substantially de-risked" and likely to contribute to growth before 2030 [2] Group 2 - Novartis revised its mid-term sales target for 2025-2030 to a CAGR of 5-6% in constant currencies and aims to achieve margins above 40% by 2029, despite a projected 1-2 percentage points dilution from the acquisition of Avidity Biosciences [3] - The company is focused on discovering, developing, and manufacturing innovative treatments aimed at improving and extending lives while addressing serious diseases [4]

Summary of Key Points from the Conference Call on Small Nucleic Acid Drugs Industry Overview - The discussion centers around the small nucleic acid drug industry, highlighting its advantages over traditional drug platforms and the potential for various applications in treating diseases. Core Insights and Arguments 1. **Efficacy and Mechanism**: Small nucleic acid drugs can reduce protein expression levels by over 80%-90%, significantly outperforming small molecule and antibody drugs, which only lower activity or clear existing proteins [2][5][8] 2. **Long-lasting Effects**: Some small nucleic acid therapies require administration only once every six months, showcasing their long-lasting effects and low resistance development [2][5] 3. **Delivery Technologies**: The Golang liver delivery technology is currently the mainstream method but is limited to liver applications. New strategies involving peptide and antibody modifications aim to expand delivery beyond the liver [3][4] 4. **Multi-target Strategies**: The potential of multi-target strategies in drug development is significant, as demonstrated by Novartis' Inclisiran, which generated $790 million in revenue in the first three quarters of the year [5][8] 5. **Emerging Markets**: There is a growing market for small nucleic acid drugs in obesity treatment, with drugs like GPS-75 showing promise in altering the current weight loss market dynamics [9][20] 6. **Rare Diseases and CNS Applications**: Small nucleic acid drugs show potential in treating rare diseases and central nervous system disorders, with Novartis' acquisition of RVDP technology indicating strong confidence in muscle disease treatments [8][11] 7. **Challenges in Delivery**: The complexity of delivery systems poses significant barriers to entry for new companies, as effective delivery tools are crucial for the success of small nucleic acid therapies [12][22] 8. **Chemical Modifications**: Chemical modifications are essential for enhancing the stability and bioavailability of small nucleic acids, although current methods do not create significant barriers to entry [13][14] 9. **Market Potential**: The market for small nucleic acid drugs in treating cardiovascular diseases is substantial, as indicated by the $12 billion acquisition of a muscle treatment drug by Novartis [10][22] Other Important Insights 1. **Clinical Trials and Data**: Ongoing clinical trials, such as Wave 007, are showing promising results in weight loss applications, indicating a trend towards combining small nucleic acid drugs with existing therapies like GLP-1 [20][21] 2. **Regulatory and Safety Considerations**: The design of small nucleic acid sequences must consider potential off-target effects, necessitating thorough testing to ensure safety [18][25] 3. **Domestic Innovations**: Domestic companies like Shengyin, Bowang, and Ruibo are making significant strides in small nucleic acid research, with collaborations and innovations that enhance their market positions [28] This summary encapsulates the key points discussed in the conference call, providing a comprehensive overview of the small nucleic acid drug industry, its current state, and future potential.

Core Insights - Novartis announced the approval of its innovative drug, Rimegepant (Rimebuntin Tablets), by the National Medical Products Administration for adults with chronic spontaneous urticaria (CSU) inadequately controlled by H1 antihistamines [1] Group 1: Drug Approval and Market Context - Rimegepant is specifically indicated for adult patients suffering from CSU, a condition characterized by hives, itching, or angioedema occurring daily or intermittently for more than six weeks [1] - CSU is the most common type of chronic urticaria, with over 10 million patients in China [1] - More than 50% of CSU patients do not achieve effective symptom control with standard doses of H1 antihistamines [1] Group 2: Clinical Trial Results - The approval of Rimegepant is based on the results of two pivotal Phase III global multicenter clinical trials, REMIX-1 and REMIX-2 [1] - Patients with CSU who continued to experience symptoms after treatment with second-generation antihistamines showed significant clinical improvement within one week of starting Rimegepant, with effects lasting up to 52 weeks [1] Group 3: Regulatory Process - The application for Rimegepant's market authorization was formally accepted by the National Medical Products Administration in February of this year and was prioritized for review, leading to its approval within nine months [1]

Group 1: Market Overview - Pluvicto has become a major topic in the nuclear medicine field, with sales projected to reach $1.392 billion in 2024, a 42% increase year-over-year [1] - The sales of Pluvicto for the first three quarters of this year reached $1.389 billion, reflecting a 33% year-over-year growth [1] - Novartis predicts that Pluvicto's peak sales will exceed $5 billion [1] Group 2: Competitive Landscape - Major pharmaceutical companies such as Eli Lilly, BMS, AstraZeneca, and Roche are actively entering the nuclear medicine market [2][5] - Domestic companies like Heng Rui and Chengdu Nuyret are also making significant strides in nuclear medicine research and development [2][6] - The market is experiencing a new wave of growth, particularly in radiolabeled drug conjugates (RDC) [2][5] Group 3: Clinical Developments - Novartis leads the nuclear medicine sector with multiple products, including Lutathera and Pluvicto, and is developing additional candidates like 177Lu-NeoB and 225Ac-PSMA-617 [5][6] - Several domestic companies have products in late-stage clinical trials, such as ITM-11 and NRT6003, targeting various cancers [6][11] - The clinical pipeline for 177Lu-based products is expanding, with 17 innovative drug products currently in clinical stages in China [9] Group 4: Supply Chain and Production - The supply chain for Lu-177 has seen significant improvements, with domestic production capabilities being established to meet market demand [13][14] - The launch of the core product Lu-177 by Hefu One on June 25, 2025, marks a major breakthrough in the domestic production of medical isotopes [13] - The integration of nuclear medicine production and supply chains is becoming more evident, particularly in regions like Sichuan and Haiyan [23] Group 5: Future Trends - Research is expanding into new alpha-emitting isotopes, with a focus on Ac-225, which has shown promise in treating various cancers [15][17] - The supply chain challenges for Ac-225 are more severe than those for Lu-177, with a significant gap between production and clinical demand [22] - The nuclear medicine sector is entering a new phase of rapid growth, driven by advancements in both research and production capabilities [24]

Core Insights - The approval of Itvisma by the FDA marks a significant advancement in gene therapy for spinal muscular atrophy (SMA), targeting patients aged two and older with specific genetic mutations [1][2] - Itvisma's wholesale price is set at $2.59 million, making it one of the most expensive drugs on the market, and it is the first gene therapy approved for a broader patient demographic [1][3] - The global gene therapy market is expected to grow at an annual rate of over 20% in the next 5-10 years, driven by technological advancements and regulatory clarity [2][8] Drug Pricing and Market Strategy - Novartis has justified the high pricing of Zolgensma, its previous gene therapy, citing a total R&D investment of $9.4 billion, including an $8.7 billion acquisition of AveXis [3][4] - The pricing strategy for Zolgensma has been significantly higher than industry estimates, indicating a potential trend for future gene therapies [3][4] - Itvisma's pricing reflects a calculated commercial strategy, aiming to establish a precedent for high-cost life-saving treatments [3][4] Competitive Landscape - Itvisma competes directly with Spinraza, the first targeted SMA treatment, which has undergone significant price reductions in China after being included in the national insurance directory [6][7] - The gene therapy market is characterized by high R&D costs and significant barriers to entry, allowing early entrants to maintain pricing power and market exclusivity [2][7] - The market is expected to evolve towards platform-based and diversified pipelines as more companies enter the gene editing and delivery systems space [2][8] Market Growth and Investment - The global gene therapy market is projected to reach $9.03 billion in 2024 and grow to $64.64 billion by 2033, with a compound annual growth rate of 27.6% [8] - Major pharmaceutical companies are actively investing in gene therapy, with significant acquisitions and partnerships to enhance their portfolios [9][10] - The increasing number of approved gene therapy products and the rapid pace of regulatory approvals are expected to drive market expansion [8][10] Challenges and Future Directions - The development of gene therapies faces challenges such as high costs, short shelf life, and production capacity limitations [11][12] - The industry is exploring second and third-generation gene therapies to overcome the limitations of current technologies, such as AAV delivery systems [11][12] - Balancing innovation incentives with drug accessibility remains a long-term issue for the industry [11][12]