Xencor (NasdaqGM:XNCR) FY Conference December 02, 2025 02:00 PM ET Company ParticipantsDane Leone - EVP and Chief Strategy OfficerBassil Dahiyat - Co-founder, President, and CEOConference Call ParticipantsTed Tenthoff - Senior Biotech AnalystTed TenthoffTed Tenthoff, I'm a Senior Biotech Analyst at Piper Sandler, and before I begin, I'm required to point out certain disclosures regarding the relationship between Piper and our next presenting company, Xencor, which are located in the back of the room and the ...

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]