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.

Core Insights - Xencor is advancing its clinical trial programs with two first-in-class bispecific antibodies, XmAb819 and XmAb541, targeting specific cancer types, showing promising initial results [1][7] - The company reported significant revenue growth in Q2 2025, primarily from milestone payments and royalties, indicating a strong financial position despite not having marketed drugs [2] - Xencor has a diverse pipeline with over a dozen drug candidates at various development stages, showcasing its robust research capabilities [3][4] Group 1: Clinical Development - XmAb819 targets clear cell renal cell carcinoma (ccRCC) and has shown a 25% overall response rate in heavily pretreated patients during Phase 1 trials [1] - XmAb541 is under evaluation for advanced solid tumors expressing CLDN6, with ongoing Phase 1 dose escalation studies [7] - The company plans to recommend a Phase 3 dose for XmAb819 next year and initiate pivotal studies by 2027 [1] Group 2: Financial Performance - Xencor's Q2 2025 revenue reached $43.6 million, an 82% increase compared to Q2 2024, driven by milestone payments and non-cash royalties [2] - The company does not market any approved drugs directly but benefits from royalties on licensed products [2] Group 3: Analyst Sentiment - Despite a 39% decline in stock price year-to-date, analysts like Barclays's Etzer Darout have upgraded Xencor to Overweight, citing positive updates on its pipeline [8][9] - The consensus rating for Xencor stock is Strong Buy, with 12 Buy ratings and a price target suggesting an 85% potential gain over the next 12 months [11]

XmAb819 Clinical Trial - Key Findings - The Phase 1 dose-escalation study of XmAb819 in ccRCC showed a manageable safety profile, with most CRS events being Grade 1/2 and occurring during priming [47, 51, 136] - Correct dose preparation resulted in 4% Grade 3 CRS (2/51), while dose preparation errors led to 28% Grade 3 CRS (5/18) [40, 136] - In the target dose range, correct dose preparation resulted in 6% Grade 3 CRS (1/18), while dose preparation errors led to 50% Grade 3 CRS (3/6) [40, 136] - XmAb819 demonstrated an objective response rate (ORR) of 25% (95% CI: 9-49) and a disease control rate (DCR) of 70% (95% CI: 46-88) in the efficacy-evaluable target dose range (N=20) [55, 89, 125] - The median number of prior regimens for patients in the XmAb819 study was 4 (range: 1-8), with 70% having received ≥3 prior regimens [35, 89, 119] XmAb819 Development & Market Opportunity - Xencor is planning to start a pivotal study of XmAb819 as monotherapy in advanced ccRCC in 2027 [79, 104] - The global RCC market is expected to reach approximately $12 billion by 2030 [80] - In the U S, there are approximately 60,000 new cases of ccRCC per year [84] XmAb541 Early Results - Early data from the Phase 1 dose escalation study of XmAb541 showed promising anti-tumor activity in advanced ovarian cancer, endometrial cancer, and germ cell tumors [4, 93, 97] - The total sales in 1H25 for ovarian cancer drugs were $338 million, and for endometrial cancer drugs were $196 million [100]

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]