Summary of Zencore Conference Call Company Overview - **Company**: Zencore - **Event**: Cantor Global Healthcare Conference - **Date**: September 04, 2025 Key Points Current State and Strategy - Zencore is focused on developing drugs for severe diseases using its XmAb Protein Engineering Platform, targeting unmet needs in both oncology and autoimmune diseases [3][4] - The company is advancing into immunology indications, building on its core oncology expertise [2][3] Bispecific T Cell Engager Program - The XmAb819 bispecific T cell engager targets ENPP3, a protein expressed in renal cell carcinoma (RCC) and other solid tumors [6][10] - Initial data from the dose escalation phase is expected to be presented at the AACR NCI EORTC meeting in October 2025 [10][18] - The program aims to provide a differentiated treatment option in a complex therapeutic landscape for RCC, where existing therapies have limitations [13][14] Clinical Landscape for RCC - Current first-line treatments for advanced clear cell RCC include PD-1 inhibitors and VEGF TKIs, with a lack of effective options for patients who progress beyond second-line therapy [13][14] - Belzutafan, a recently approved therapy, has shown a 25% response rate in heavily pretreated patients, indicating a need for more effective treatments [15][16] TL1A Asset Development - Zencore is developing TL1A as a potential best-in-class molecule for inflammatory bowel disease (IBD) and other indications [22][23] - The company is initiating a Phase 2b study in ulcerative colitis, with plans to explore additional indications like Crohn's disease [24][28] - The TL1A program is positioned to capitalize on the limitations of existing therapies, aiming for improved efficacy and patient outcomes [27][28] Bispecific Antibody Approach - Zencore is exploring bispecific antibodies targeting TL1A and IL-23, with potential applications in IBD and other autoimmune diseases [29][30] - The bispecific approach is expected to offer a safer profile and improved dosing flexibility compared to existing therapies [29][34] Future Outlook - Zencore plans to continue leveraging its engineering tools to develop novel drug candidates while focusing on clinical data generation [51][52] - The company is optimistic about the potential of its current pipeline, particularly in the context of unmet medical needs in oncology and autoimmune diseases [18][52] Additional Insights - The company acknowledges the challenges in modeling drug exposure in the gut for IBD therapies, emphasizing the need for high drug exposure to achieve desired clinical outcomes [39][42] - Zencore is committed to exploring the therapeutic potential of B cell depletion in autoimmune diseases, drawing parallels with successful oncology therapies [45][48] Conclusion - Zencore is strategically positioned to advance its innovative therapies in oncology and immunology, with a strong focus on addressing unmet medical needs through its proprietary engineering platform and clinical development programs [51][52]

Financial Data and Key Metrics Changes - The company is at a clinical inflection point with a focus on oncology and autoimmune disease programs, indicating a strategic reset and a shift towards higher probability success programs [4][5] - The Phase 2b study for the monospecific TL1a program in ulcerative colitis has commenced, with expectations for significant data generation in the coming years [6][7] Business Line Data and Key Metrics Changes - The company has three therapeutic verticals: oncology, autoimmune diseases, and a focus on protein engineering to enhance drug modalities [6][7] - XmAb942, targeting TL1a, has shown a greater than seventy-one day half-life, allowing for a Q12 week dosing schedule, which is a significant improvement over first-generation drugs [12][18] Market Data and Key Metrics Changes - The company is targeting advanced clear cell renal cell carcinoma with XmAb819, which has a high unmet need for innovative treatments [36][40] - The competitive landscape includes other companies developing TL1a and IL-23 inhibitors, with the company aiming to differentiate its products through superior potency and dosing schedules [13][21] Company Strategy and Development Direction - The company aims to leverage its protein engineering platform to create differentiated therapies that maximize patient benefits and advance the standard of care [6][7] - A strategic reset in September 2024 has set the stage for clinical data generation and regulatory approvals, with a focus on bringing the story together for investors [46][47] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical development pipeline and the potential for differentiated clinical profiles that could lead to successful commercialization [19][41] - The company is focused on efficient study designs to expedite the transition to pivotal studies and commercialization [19][33] Other Important Information - The company has initiated multiple clinical studies, including the bispecific TL1A and IL-23 program, with first-in-human studies expected in 2026 [22][24] - The company is also ramping up studies for plamotamab and XmAb657, with regulatory authorizations in progress [26][27] Q&A Session Summary Question: Can you discuss the rationale for targeting ENPP3 in CCRC patients? - The company chose ENPP3 based on internal data and third-party validation, allowing for a faster study design without preselecting patients [36][38] Question: What are the advantages of the bispecific design over combining an anti-TL1A with an IL-23? - The bispecific design allows for a synergistic effect between TL1A and IL-23, potentially leading to better clinical outcomes with a single drug delivery [21][22] Question: What is the expected timeline for initial data readout for plamotamab? - Initial data is expected towards the end of this year or early next year as the study ramps up [33] Question: How does the company plan to differentiate XmAb541 from other therapies? - The company aims to achieve a favorable safety profile and effective dosing regimen to differentiate XmAb541 from existing therapies targeting CLDN6 [44][45]

XmAb Technology and Pipeline - Xencor's XmAb platform is used to engineer antibodies with enhanced properties, focusing on oncology and autoimmune diseases[4, 9, 10] - The pipeline includes T-cell engagers and bispecific antibodies targeting various cancers and autoimmune conditions, such as IBD and rheumatoid arthritis[10, 11] - Key programs include XmAb942 (TL1A inhibitor) for IBD, Plamotamab (CD20xCD3) for rheumatoid arthritis, and XmAb819 (ENPP3 x CD3) for ccRCC[11, 12] XmAb942: Anti-TL1A Antibody for IBD - XmAb942 is designed for potent TL1A inhibition, convenient subcutaneous dosing, and extended half-life, potentially enabling Q12W maintenance dosing[31] - Phase 1 study in healthy volunteers showed a +71 day estimated half-life and dose-dependent increases in total TL1A, supporting less frequent dosing[31, 45] - Phase 1 data also showed rapid and sustained reduction of free sTL1A below the lower limit of quantification (LLOQ) for at least 16 weeks from a single dose[49] XmAb942 Clinical Development and Market Opportunity - A Phase 2 study (XENITH-UC) in ulcerative colitis is planned, with a design to maximize drug exposure and potentially achieve greater efficacy[56, 61] - The global IBD drug market is projected to exceed $23 billion by 2030, with anti-TL1A therapies expected to capture a significant portion[14, 74] - Gastroenterologist surveys indicate high expected utilization of anti-TL1A drugs, with approximately 9 out of 10 expecting to use them as first or second-line advanced therapy[74] XmAb TL1A x IL23 Bispecific Program - Xencor is developing XENP53***, a TL1A x IL23p19 bispecific antibody, with lead candidate selection and GMP production underway for a planned first-in-human study in 2026[11, 71] - Preclinical data suggests competitive functional potency for both TL1A and IL23 inhibition compared to other agents[69, 70] Financial Position - Xencor reported $706.7 million in cash, cash equivalents, and marketable debt securities as of December 31, 2024, supporting the development and expansion of the TL1A program[89]

Summary of Xencor (XNCR) Update / Briefing April 29, 2025 Company Overview - **Company**: Xencor (XNCR) - **Focus**: Development of protein engineering and drug molecules for unmet medical needs, particularly in oncology and immunology Key Industry Insights - **Industry**: Inflammatory Bowel Disease (IBD) treatment - **Current Market Need**: High unmet medical need in IBD, with existing medications achieving remission in only 10% to 20% of patients [7][8] - **Target Population**: Over 3 million individuals affected by IBD in the U.S. and Europe [7] Core Program Updates - **XmAb942**: A high potency, half-life extended anti-TL1A antibody - **Phase I Study Results**: Positive interim results indicating safety and pharmacokinetics [2][12] - **Half-Life**: Estimated at greater than 71 days, promising for convenient dosing [14] - **Dosing Schedule**: Planned Q12 week subcutaneous maintenance dosing [11][21] - **TL1A by IL-23 P19 Bispecific**: A lead candidate designed to combine two effective mechanisms of action for IBD treatment - **Development Timeline**: First in human studies expected in 2026 [58] Clinical Development Plans - **Phase II Study (ZENITH UC)**: - Focus on patients with moderately to severely active ulcerative colitis who have failed previous therapies [19][21] - Primary endpoint: Clinical remission based on modified Mayo Score at week twelve [21] - Expected to start in the second half of 2025 [61] Competitive Landscape - **Comparison with Competitors**: XmAb942 expected to provide higher drug exposure and better clinical outcomes compared to leading first-generation anti-TL1A drugs [60] - **Dosing Frequency**: Over 90% of surveyed gastroenterologists believe that XmAb942's Q12 week dosing could significantly improve patient compliance [61] Future Directions - **Combination Therapies**: Emphasis on developing a combination strategy with IL-23 and TL1A targeting to enhance efficacy [49][54] - **Market Positioning**: Xencor aims to position XmAb942 as a first or second line treatment option in advanced IBD therapy [60] Important Considerations - **Safety Profile**: No significant safety signals observed in Phase II data for competing therapies [31] - **Patient Compliance**: A more convenient dosing schedule is expected to improve patient quality of life and adherence to treatment [42][43] Conclusion - Xencor is advancing its pipeline with promising data for XmAb942 and a bispecific candidate targeting TL1A and IL-23, aiming to address significant unmet needs in IBD treatment while enhancing patient experience through improved dosing regimens and safety profiles [66]