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Financial Data and Key Metrics Changes - In Q4 2025, total revenue was approximately $12.5 billion, flat year-over-year, while the growth portfolio revenue increased by 15% to $7.4 billion, representing nearly 60% of total revenue [14][15] - For the full year, the growth portfolio grew 17%, offsetting a decline of roughly $4 billion in revenue from the legacy portfolio [6][7] - Adjusted diluted earnings per share for Q4 were $1.26, and for the full year, it was $6.15, both including a net charge related to in-process R&D and licensing income [20] Business Line Data and Key Metrics Changes - Opdivo revenue grew 7% to nearly $2.7 billion in Q4, driven by new indications and share growth in first-line non-small cell lung cancer [15] - Reblozyl achieved 21% growth, reflecting solid uptake across MDS-associated anemia patients [16] - Breyanzi's revenue increased by 47% in Q4, driven by strong demand across its approved indications [16] - Eliquis revenue was nearly $3.5 billion in Q4, up 6%, supported by demand growth and market share gains [16] Market Data and Key Metrics Changes - The U.S. market for Eliquis saw a 4% revenue increase, contributing to its overall growth [16] - Camzyos revenue grew 57% to $353 million in Q4, benefiting from global demand growth [17] - Sotyktu's global revenue grew 3%, with upcoming PDUFA dates for psoriatic arthritis and phase III readouts for lupus and Sjögren's disease [17] Company Strategy and Development Direction - The company aims to deliver industry-leading sustainable growth into the 2030s, focusing on executing its growth strategy and advancing its pipeline [11][23] - A multi-year plan is in place to rewire the company for long-term growth, with expectations to introduce over 10 new medicines and 30 meaningful launch opportunities by 2030 [9][10] - The company is expanding the use of AI to enhance operational efficiency and reinvest strategically in growth [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth portfolio's ability to drive revenue despite anticipated declines in the legacy portfolio due to ongoing LOE impacts [12] - The company expects 2026 revenue in the range of $46-$47.5 billion, with a projected decline of 12%-16% in the legacy portfolio [12][21] - Management highlighted the importance of maintaining a strong say-to-do ratio and delivering on commitments as part of the company culture [11] Other Important Information - The company completed a targeted $10 billion debt paydown ahead of schedule and generated strong cash flow from operations of approximately $2 billion in Q4 [20] - The effective tax rate for Q4 was 22.1%, reflecting a one-time non-tax deductible in-process R&D charge related to the Orbital acquisition [19] Q&A Session Summary Question: Insights on pivotal catalysts for 2026 - Management highlighted the potential for over 10 phase III data readouts this year, with a focus on products like Milvexian and Admilparant [25][28] Question: Eliquis dynamics for 2026 - Eliquis is expected to grow 10%-15% in 2026, driven by market share gains and pricing strategy adjustments [39] Question: Business development priorities - The company is focused on deepening its presence in existing therapeutic areas while remaining opportunistic for new opportunities [37] Question: Milvexian AFib study updates - The study is progressing well, with a focus on demonstrating non-inferiority to Eliquis and potential benefits in bleeding risks [46] Question: Admilparant's hypotension risk - Management indicated that the hypotension risk is being well managed in the phase three studies, with a focus on higher dosing [89]

Core Insights - Caribou Biosciences, Inc. is presenting clinical data on its allogeneic CAR-T cell therapies, vispa-cel and CB-011, at the 2026 Tandem Meetings, highlighting their potential in treating relapsed or refractory hematologic malignancies [1][2][3] Group 1: Clinical Trials and Data - The ANTLER phase 1 clinical trial for vispa-cel shows outcomes comparable to autologous CAR-T therapies in patients with relapsed/refractory B cell non-Hodgkin lymphoma [5][6] - The CaMMouflage phase 1 clinical trial for CB-011 demonstrates a correlation between CAR-T cell expansion and durable responses in patients with relapsed/refractory multiple myeloma [5][8] - A total of 84 patients have been treated in the ANTLER trial, with a recommended phase 2 dose of 80x10^6 CAR-T cells selected [6] Group 2: Product Information - Vispa-cel is the first allogeneic CAR-T cell therapy with a PD-1 knockout, aimed at enhancing CAR-T cell activity by reducing exhaustion [4][9] - CB-011 employs an immune cloaking strategy with a B2M knockout and a B2M–HLA-E fusion protein to mitigate immune rejection [7][9] - Both therapies have received Fast Track and Orphan Drug designations from the FDA, indicating their potential to address unmet medical needs [4][7] Group 3: Company Overview - Caribou Biosciences focuses on developing transformative therapies using its CRISPR genome-editing platform, aiming to improve access to cellular therapies for patients with severe diseases [9] - The company emphasizes the potential of its off-the-shelf CAR-T cell therapies to provide rapid treatment options for patients with hematologic malignancies [9]

Company Updates - Legend Biotech Corporation will present the latest company updates at the 44th Annual J.P. Morgan Healthcare Conference on January 14, 2026, at 9:00 a.m. PT [1] - The live webcast of the presentation will be accessible through the Investor Relations section of Legend's website, with a replay available approximately 48 hours later [2] Company Overview - Legend Biotech is the largest standalone cell therapy company with over 2,900 employees and is a pioneer in cancer treatment innovations [3] - The company is leading the CAR-T cell therapy revolution with its product CARVYKTI, a one-time treatment for relapsed or refractory multiple myeloma, developed in collaboration with Johnson & Johnson [3] - Legend Biotech aims to maximize patient access and therapeutic potential of CARVYKTI while driving future innovations across its pipeline of advanced cell therapy modalities [3]

Core Insights - Legend Biotech Corporation announced long-term clinical data for CARVYKTI, showing a median progression-free survival (mPFS) of 50.4 months in triple-class-exposed relapsed/refractory multiple myeloma patients after a single infusion, marking one of the longest PFS outcomes for BCMA-targeted CAR-T therapy in this population [1][8][12] Group 1: Clinical Data and Efficacy - The CARTITUDE-1 and CARTITUDE-4 studies demonstrated that patients treated with CARVYKTI earlier in their treatment journey exhibited stronger immune fitness and a more immunocompetent tumor microenvironment, correlating with longer PFS [3][4][12] - At a median follow-up of 33.6 months, patients with standard-risk cytogenetics in the CARVYKTI arm achieved a 30-month PFS rate of 71.0%, compared to 43.2% in the standard-of-care arm [7][8] - Notably, all patients who achieved minimal residual disease (MRD)-negative complete response at 12 months following CARVYKTI infusion remained progression-free at 30 months [9] Group 2: Safety and Adverse Events - Among patients receiving CARVYKTI, cytokine release syndrome (CRS) occurred in 84% of cases, with a median time to onset of 7 days and resolution in 82% of patients [20][22] - Neurologic toxicities, including Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS), occurred in 24% of patients, with a median time to onset of 10 days [25][28] - Hypogammaglobulinemia was reported in 36% of patients, with 93% experiencing laboratory IgG levels below 500 mg/dL after infusion [52][53] Group 3: Company Overview and Future Directions - Legend Biotech is a leader in cell therapy, particularly with CARVYKTI, which has been approved for treating relapsed or refractory multiple myeloma [64][65] - The company is focused on expanding patient access and therapeutic potential of CARVYKTI while driving innovation across its pipeline of cell therapy modalities [71]

Summary of Chimeric Therapeutics Update / Briefing Company Overview - **Company**: Chimeric Therapeutics (ASX:CHM) - **Focus**: Development of CAR-T cell therapies, specifically targeting CDH17 for neuroendocrine tumors and other cancers - **Current Trials**: Four active phase one clinical trials under three different FDA INDs across multiple U.S. centers [1][2] Core Points and Arguments - **Lead Program**: CHM 2101 is the first CDH17 CAR-T in clinical trials under an FDA IND, with significant potential in the CDH17 space [2][10] - **Clinical Trials**: - The IND was cleared in November 2023, and fast track status was granted in April 2025, facilitating real-time interaction with the FDA [10][11] - Currently enrolling patients with colorectal cancer, gastric cancer, and neuroendocrine cancers [11] - Eight patients have been treated so far, with plans to treat a total of 15 in the phase one study [11][12] - **Study Design**: The trial is flexible and adaptive, exploring three dose levels, with safety established at the first dose level of 50 million CAR-T cells [12][14] - **Efficacy Indicators**: Early signs of anti-tumor activity observed, including a 12% tumor shrinkage in one patient at dose level two [17] Leadership and Expertise - **Leadership Team**: Includes experienced professionals with backgrounds in CAR-T therapies from companies like Amgen, Celgene, and Kite Pharma [3][4] - **Clinical Expertise**: Dr. Jennifer Eads, a key figure in the trial, emphasizes the importance of quality of life for patients with neuroendocrine tumors and the strategic approach to treatment [22][25] Clinical Experience and Patient Outcomes - **Patient Profiles**: Focus on patients with stable disease who have progressed on standard somatostatin analog therapy [25] - **Cytokine Release Syndrome (CRS)**: Two patients experienced CRS, which is being monitored closely; it can indicate immune activation [34][36] - **Quality of Life Improvements**: One patient reported significant improvements in quality of life post-treatment, highlighting the potential benefits of CAR-T therapy [29] Market Potential - **Market Size**: The global market for CAR-T therapies was approximately $27 billion last year and is expected to grow significantly, particularly due to rising bowel cancer rates among younger populations [43] - **Commercial Opportunities**: Interest from big pharma companies in CAR-T therapies presents potential partnerships and licensing opportunities [46] Safety and Regulatory Considerations - **Safety Monitoring**: Ongoing assessment of safety and efficacy is critical, with a focus on balancing treatment benefits against potential side effects [49][50] - **Regulatory Pathway**: Fast track designation allows for potential market entry at the end of phase two, reducing the need for extensive phase three trials [45] Conclusion - **Progress and Future Outlook**: Chimeric Therapeutics is optimistic about the ongoing trials and the potential for CHM 2101 to provide significant benefits to patients with neuroendocrine tumors and other cancers, with more data expected in the coming weeks [44][51]

Core Viewpoint - The article discusses the development and potential of in vivo CAR-T cell therapy, particularly focusing on Capstan Therapeutics and its innovative approach to treating cancer and autoimmune diseases through a new mRNA delivery system [2][3][19]. Group 1: In Vivo CAR-T Technology - In vivo CAR-T technology allows for the generation of CAR-T cells directly within the body through the injection of lipid nanoparticles (LNP) delivering mRNA, addressing challenges such as complexity, time, and cost associated with traditional CAR-T therapies [2][3]. - Capstan Therapeutics, founded by leading researchers in the field, has secured $340 million in funding to advance this technology for various diseases [2][3]. Group 2: Clinical Trials and Research Findings - Capstan's CAR-T therapy CPTX2309 has commenced Phase 1 clinical trials for treating B cell-mediated autoimmune diseases [3]. - Preclinical studies demonstrated that the proprietary targeted lipid nanoparticles (tLNP) effectively delivered CAR mRNA to CD8+ T cells, showing promising therapeutic prospects and safety in animal models [3][4]. Group 3: Market Potential and Patient Demographics - The patient population for autoimmune diseases is significantly larger than that for B cell malignancies, with approximately 20 million individuals in the U.S. and 10% of the global population affected [6]. - There is a pressing need for scalable, off-the-shelf therapies that do not require chemotherapy preconditioning and can be administered in non-specialized medical centers [6]. Group 4: Mechanism and Efficacy - The research team developed a novel ionizable lipid L828 and optimized the LNP formulation to enhance targeting and accumulation in the liver while minimizing off-target effects [7]. - The CD8-L829-tLNP demonstrated a preference for modifying CD8+ T cells over CD4+ T cells, leading to effective targeting and destruction of B cells in both humanized mouse models and non-human primate models [9][10]. Group 5: Safety and Tolerability - In non-human primate studies, the treatment showed good tolerability, although some adverse effects were noted, such as a known side effect of CAR-T therapy [16]. - The study indicated that the treatment led to a temporary depletion of B cells, suggesting a reset of the immune system, which is crucial for long-term therapeutic benefits [16][19].

Core Insights - Legend Biotech Corporation reported strong commercial performance of CARVYKTI, aiming for company-wide profitability by next year through capacity expansion and global approvals [2][6][10] Regulatory Updates - The European Medicines Agency's CHMP provided a positive opinion for CARVYKTI, highlighting significant improvement in overall survival from the CARTITUDE-4 study [7] - Australia's TGA approved CARVYKTI for second-line treatment in multiple myeloma patients [7] Key Business Developments - Over 6,000 patients have been treated with CARVYKTI to date [6] - Clinical production of CARVYKTI was initiated at the Tech Lane facility in Belgium, with commercial production expected by the end of 2025 [6][7] - The company published its second annual ESG report, aligning with various sustainability standards [7] First Quarter 2025 Financial Results - CARVYKTI net trade sales reached approximately $369 million [6] - Total revenue for Q1 2025 was $195.1 million, up from $94.0 million in Q1 2024 [14] - Collaboration revenue increased to $185.6 million from $78.5 million year-over-year [12] - License revenue decreased to $9.3 million from $12.2 million year-over-year [12] - Net loss for Q1 2025 was $100.9 million, compared to a net loss of $59.8 million in Q1 2024 [12][15] - Cash and cash equivalents stood at $1.0 billion as of March 31, 2025, providing a financial runway into Q2 2026 [6][12]

Company Overview - Legend Biotech Corporation is a global leader in cell therapy with over 2,500 employees, making it the largest standalone cell therapy company [3] - The company is pioneering treatments that aim to revolutionize cancer care, particularly through its CAR-T cell therapy [3] - CARVYKTI, a one-time treatment for relapsed or refractory multiple myeloma, is developed and marketed in collaboration with Johnson & Johnson [3] Upcoming Events - Legend Biotech will host a conference call for investors on May 13, 2025, at 8:00 am ET to review first-quarter 2025 results [1] - Senior leaders will provide an overview of the company's performance during the call [1] - A replay of the webcast and earnings news release will be available approximately two hours after the call concludes [2]

Core Viewpoint - Mustang Bio, Inc. has exited its lease for a manufacturing facility in Worcester, Massachusetts, and divested certain fixed assets to AbbVie for $1.0 million, while relocating its corporate headquarters to Waltham, Massachusetts [1][2]. Group 1: Financial Implications - The termination of the lease is expected to result in approximately $2.0 million in cash expense savings over the next 24 months [2]. - The divestment of fixed assets to AbbVie Bioresearch Center Inc. was completed for a total of $1.0 million [1]. Group 2: Strategic Focus - The company remains committed to advancing its existing portfolio and plans to initiate a novel clinical trial with MB-109, targeting recurrent glioblastoma and high-grade astrocytomas in the second half of 2025 [3]. - MB-109 is a combination therapy that includes MB-101 (IL13Rα2-targeted CAR-T cell therapy) and MB-108 (HSV-1 oncolytic virus), aimed at enhancing the efficacy of CAR-T cell therapy by modifying the tumor microenvironment [4]. Group 3: Company Overview - Mustang Bio is a clinical-stage biopharmaceutical company focused on developing cell therapies for difficult-to-treat cancers, partnering with leading medical institutions to advance CAR-T therapies [5].