Q4 '25 Earnings Call February 3, 2026 Safe Harbor Statement This presentation contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeOne Medicines Ltd. or Kyowa Kirin Co., Ltd.), the performance o ...

Core Viewpoint - TCE's efficacy and commercialization capabilities in hematological malignancies have been fully validated, but several challenges remain for its widespread application in solid tumors [1] Group 1: Current Status of TCE - A total of 12 TCE therapies have been approved globally, with 10 in the US and 6 in China; 9 are for hematological malignancies and only 3 for solid tumors [1] - The application of TCE in solid tumors faces challenges such as targeting tumor-associated antigens (TAA) without harming healthy tissues, enhancing T cell infiltration in the tumor microenvironment, and overcoming immunosuppressive cells and cytokines that lead to T cell exhaustion [1] Group 2: Design Innovations Enhancing TCE Applicability - Non-full-length bispecific antibodies and 2+1 format designs have shown promise; Amgen's DLL3/CD3 bispecific antibody has been approved for SCLC, and MSD's Gocatamig has demonstrated high tumor response rates in later-line SCLC patients [2] - The "2+1" format design allows for precise control of CD3 affinity, with Xencor's XmAb platform advancing its pipeline to Phase III clinical trials [2] - TCR therapy, exemplified by Immunocore's KIMMTRAK, targets intracellular protein antigens and has received FDA approval for uveal melanoma, with potential for expansion into other indications [2] Group 3: Strategies to Mitigate Toxicity and Enhance Efficacy - Prodrug designs are being explored to reduce off-target toxicity; Janux has validated its TCE in clinical settings, and Vir's VIR-5818 shows promising initial data in HER2-positive breast cancer [3] - Co-stimulatory signals from CD28, 4-1BB, and CD2 are expected to enhance TCE responses; Regeneron's CD28 bispecific antibody strategy has shown effectiveness but raised safety concerns [3] - Selective T cell activation targets are being developed to avoid broad T cell activation risks; AstraZeneca and LavaTherapeutics are working on TCEs that selectively target CD8+ T cells and Vγ9Vδ2 T cells [4] Group 4: Domestic Companies and Pipeline Development - Domestic companies are advancing TCE research with diverse technical paths, including CD28 co-stimulatory bispecific antibodies and TCR therapies, forming a robust pipeline [5] - Companies to watch include Zai Lab, Wuxi Biologics, Heng Rui Medicine, Bai Li Tianheng, and others, indicating a rich landscape for TCE development in solid tumors [5]

Summary of Xencor Conference Call Company Overview - **Company**: Xencor - **Industry**: Biopharmaceuticals, specifically focusing on protein engineering and bispecific antibodies - **Key Executives Present**: Basil Dahiyat (Co-founder, President, CEO), Dane Leone (Executive Vice President, Chief Strategy Officer) [1][2] Core Points and Arguments Expansion into Autoimmune Diseases - Xencor is re-entering the autoimmune disease space with the development of the anti-TL1A antibody, XmAb 942, after previously focusing on oncology [3][4] - The decision to return to autoimmune diseases was driven by the potential for creating differentiated clinical assets [4] - XmAb 942 is designed for high potency and long half-life, targeting TL1A, an inflammatory cytokine linked to inflammatory bowel diseases (IBD) [5][6] Clinical Data and Studies - Phase 1 data for XmAb 942 showed a half-life of over 71 days and sustained suppression of TL1A for over 16 weeks in healthy volunteers [7] - The ongoing Phase 2b study, XENITH-UC, aims to enroll approximately 220 patients to assess clinical remission in ulcerative colitis [11] - The study is designed to facilitate a seamless transition into registration-enabling studies, aiming for a competitive time to market [9] Future Developments - XmAb 412, a bispecific antibody targeting TL1A and IL-23, is expected to enter first-in-human trials in 2026 [10][12] - The combination of TL1A and IL-23 targeting is anticipated to enhance efficacy in IBD treatment [12][13] Other Autoimmune Programs - Xencor is also developing plamotamab, a CD20/CD3 bispecific antibody for rheumatoid arthritis (RA), leveraging their oncology experience to optimize dosing regimens [14][15] - XmAb 657, another bispecific targeting CD19/CD3, is in early development stages for myositis and other indications [16][17] Oncology Developments - XmAb 819, targeting ENPP3 in renal cell carcinoma, has shown a 25% overall response rate in heavily pretreated patients [23][24] - The company plans to expand the use of XmAb 819 into colorectal and lung cancers by 2026 [23][25] - XmAb 541, targeting CLDN6 in gynecologic tumors, is also progressing with early promising data [26][27] Partnerships and Collaborations - Xencor has established partnerships with Amgen and Johnson & Johnson, focusing on bispecific antibodies and other therapeutic areas [30][31] - The partnership with Amgen includes a phase 3 trial for Xaluritamig in metastatic castration-resistant prostate cancer, with potential royalties and milestones for Xencor [30] - Future partnerships are anticipated to enhance Xencor's capabilities and market reach [34][35] Additional Important Information - Xencor aims to be a commercial company, focusing on maximizing stakeholder value through strategic clinical development and potential partnerships [34][36] - The company is well-funded through 2028, allowing for flexibility in decision-making regarding asset management and partnerships [36] This summary encapsulates the key points discussed during the conference call, highlighting Xencor's strategic direction, clinical developments, and partnership strategies in the biopharmaceutical industry.