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]

Group 1 - Xencor (XNCR) has been upgraded to a Zacks Rank 2 (Buy), indicating a positive trend in earnings estimates which is a significant factor influencing stock prices [1][3] - The Zacks rating system is based on changes in earnings estimates, which are tracked through a consensus measure from sell-side analysts, reflecting the company's earnings outlook [2][6] - The upgrade suggests that Xencor's improving earnings outlook could lead to increased buying pressure and a rise in stock price [3][5] Group 2 - The correlation between earnings estimate revisions and stock price movements is strong, particularly due to institutional investors who adjust their valuations based on these estimates [4][6] - Xencor is projected to earn -$2.87 per share for the fiscal year ending December 2025, representing a year-over-year change of 19.8%, with a 21.3% increase in the Zacks Consensus Estimate over the past three months [8] - The Zacks Rank system maintains a balanced distribution of ratings, with only the top 20% of stocks receiving a 'Strong Buy' or 'Buy' rating, indicating superior earnings estimate revisions [9][10]

Company Performance - Xencor reported a quarterly loss of $0.62 per share, which was better than the Zacks Consensus Estimate of a loss of $0.83, but worse than the loss of $0.31 per share from a year ago [1] - The quarterly report represented an earnings surprise of 25.30%, with the company previously expected to post a loss of $0.98 per share but actually reporting a loss of $0.71, resulting in a surprise of 27.55% [2] - Xencor's revenues for the quarter ended December 2024 were $52.79 million, exceeding the Zacks Consensus Estimate by 293.40%, compared to $44.69 million in the same quarter last year [3] Market Performance - Xencor shares have declined approximately 37.4% since the beginning of the year, while the S&P 500 has gained 1.3% [4] - The current consensus EPS estimate for the upcoming quarter is -$0.88 on revenues of $12.11 million, and for the current fiscal year, it is -$3.64 on revenues of $59.03 million [8] Industry Outlook - The Medical - Drugs industry, to which Xencor belongs, is currently ranked in the top 50% of over 250 Zacks industries, indicating that companies in this segment are expected to outperform those in the bottom 50% by a factor of more than 2 to 1 [9]

Drug Development and Clinical Trials - The company is focused on developing engineered antibody therapeutics for cancer and autoimmune diseases, advancing multiple drug candidates into clinical development[13]. - The XmAb 2+1 bispecific antibody format has shown potential in preclinical models, effectively targeting tumor cells while sparing normal cells[21]. - XmAb657 demonstrated over 99.98% reduction in B cells in non-human primate studies, with a half-life estimated at 15 days, indicating potential for durable B-cell depletion[23]. - The company plans to initiate a first-in-human study for XmAb657 in the second half of 2025[23]. - XmAb819 has shown initial evidence of anti-tumor activity in advanced clear cell renal cell carcinoma (ccRCC) patients, with some patients experiencing treatment durations extending beyond one year[33]. - XmAb541 is in a Phase 1 study for ovarian cancer, with the first patient dosed in April 2024[34]. - The company has paused further development of vudalimab to prioritize other pipeline programs, with safety data remaining consistent[38]. - New XmAb drug candidates, including XmAb942 and XmAb657, are being evaluated for autoimmune and inflammatory diseases[39]. - Plamotamab demonstrated encouraging clinical activity in heavily pretreated patients with advanced lymphoma, with patient enrollment in subcutaneous dose escalation cohorts completed in 2023[41]. - A Phase 1b/2a proof-of-concept study for plamotamab in rheumatoid arthritis (RA) is planned for the first half of 2025, with efficacy evaluated at week 12[42]. - XmAb7195 was reacquired in 2024, and development opportunities are being evaluated after being licensed to Aimmune Therapeutics in 2020[43]. - Xaluritamig showed a median overall survival of 17.7 months in a Phase 1 study for mCRPC, with a PSA90 rate of 45.1% observed in high-dose cohorts[50]. - Obexelimab is in a Phase 3 study for IgG4-related disease and Phase 2 studies for relapsing multiple sclerosis and systemic lupus erythematosus[51]. Financial Performance and Projections - The company has incurred significant losses since its inception and anticipates continuing to incur significant losses for the foreseeable future[168]. - For the year ended December 31, 2024, the company incurred a net loss of $232.6 million and had an accumulated deficit of $704.0 million[179]. - As of December 31, 2024, the company had $706.7 million in cash, cash equivalents, and marketable debt securities, which is expected to fund operations into 2028[184]. - The company anticipates incurring additional net losses in future years as it continues its research and development activities[180]. - The company expects its financial condition and operating results to fluctuate significantly from quarter to quarter and year to year due to various uncontrollable factors[172]. - The company may require additional financing to support its research and development programs, which could lead to dilution of existing shareholders[168]. - The company may require additional financing to complete the clinical development of its product candidates, which may not be available on favorable terms[186]. - The market price of the company's common stock is likely to be highly volatile, influenced by various factors including market conditions and operational performance[189]. - The trading price of the company's common stock has ranged from a low of approximately $5.75 to a high of approximately $58.345 since its IPO[188]. - Approximately 56.8% of the company's voting stock is owned by executive officers, directors, and significant stockholders, allowing them to exert significant control over corporate matters[191]. Regulatory and Compliance - Regulatory compliance is critical, with extensive requirements from the FDA and other authorities for drug development, including preclinical studies and clinical trials[105][106]. - The process for obtaining FDA approval involves multiple steps, including submission of a Biologics License Application (BLA) and compliance with Good Manufacturing Practices (GMP)[107][110]. - The FDA requires that all clinical trials conducted under an IND must meet specific requirements unless waived[113]. - Clinical trials are conducted in three phases, with Phase 1 focusing on safety and dosage, Phase 2 on efficacy and safety in a larger patient population, and Phase 3 on substantial evidence of clinical efficacy and safety[115]. - The standard FDA review process for a BLA is 10 months once accepted, but it can take longer depending on various factors[121]. - The FDA may require post-marketing studies to further assess drug safety and effectiveness, which can impact the commercial value of the product[125]. - Material changes in manufacturing processes post-approval may necessitate additional regulatory review and approval[121]. - Biologic product manufacturers must comply with comprehensive FDA regulations, including cGMP compliance and periodic reporting requirements[136]. - The company is subject to extensive regulations governing the development and commercialization of its products, which may complicate compliance efforts[163]. Intellectual Property and Market Position - The company aims to expand its patent portfolio to protect its proprietary Fc technologies and drug candidates[26]. - The company has filed patent applications for thousands of specific Fc domain variants, enhancing its intellectual property position[73]. - The patent expiration for key technologies includes bispecific (2034 U.S. and Ex-U.S.) and CD3 T-Cell Engagers (2035 U.S. and Ex-U.S.)[74]. - The company relies on third-party vendors for research, development, and clinical activities, maintaining flexibility in its infrastructure[80]. - The company has agreements with KBI Biopharma and WuXi Biologics for manufacturing and development services for its antibody candidates[81][88]. - The company is developing bispecific antibody drug candidates targeting solid tumor cells and B cells, competing with major companies like Amgen, Genmab, and Roche[101][102]. - The company is also working on antibody drug candidates targeting the cytokine TL1A for potential IBD treatment, facing competition from firms like Merck and Roche[103]. Workforce and Internal Controls - As of December 31, 2024, the company had 250 full-time employees, with 203 engaged in research and development activities[64]. - The workforce was 58% non-white and 59% women as of December 31, 2024, with women making up 30% of the senior leadership team[65]. - The company completed a reduction in force (RIF) affecting approximately 10% of the total employee headcount in January 2024[66]. - The company has identified material weaknesses in its internal control over financial reporting, which could affect the accuracy and timeliness of its financial reports[168]. - The company is subject to additional internal control requirements under the Sarbanes-Oxley Act of 2002 as a large accelerated filer[200]. Market and Economic Factors - The market size for the treatment of Crohn's disease and ulcerative colitis is projected to reach $40 billion worldwide by 2032[71]. - The American Cancer Society estimates approximately 2.0 million new cases of cancer and about 618,120 cancer deaths in the U.S. by 2025[69]. - Medical expenditures for cancer in the U.S. are projected to reach at least $245.6 billion by 2030[69]. - The company is susceptible to adverse impacts from inflation and economic volatility, which could affect its financial performance[175]. - Legislative and regulatory proposals aimed at healthcare cost containment could impact the company's ability to sell product candidates profitably[150]. Stock and Shareholder Matters - The company has never declared or paid any cash dividend on its common stock and does not anticipate doing so in the foreseeable future[205]. - The company is authorized to grant equity awards covering up to 18,367,000 shares of its common stock under its equity compensation plans[195]. - The company has options to purchase 12,370,081 shares outstanding under its equity compensation plans[195]. - The company may offer and sell shares of its common stock with an aggregate offering price of up to $200 million through an ATM Offering[198]. - No shares of common stock were sold pursuant to the ATM Offering from the date of the ATM Prospectus through December 31, 2024[198]. - Provisions in the company’s charter documents may make it more difficult for third parties to acquire the company, potentially affecting stockholder value[206].

Group 1 - Xencor (XNCR) has experienced a significant decline of 21.7% over the past four weeks, but it is now in oversold territory, indicating a potential for a trend reversal [1] - The Relative Strength Index (RSI) for XNCR is currently at 27.45, suggesting that the heavy selling pressure may be exhausting, which could lead to a rebound [5] - There is a strong consensus among Wall Street analysts that XNCR will report better earnings than previously predicted, with a 1.6% increase in the consensus EPS estimate over the last 30 days [6] Group 2 - XNCR holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate revisions and EPS surprises, indicating a strong potential for a turnaround [7]

Core Viewpoint - Xencor (XNCR) has experienced a significant downtrend with a 20.3% decline over the past four weeks, but it is now in oversold territory, suggesting a potential turnaround due to improved earnings expectations from analysts [1]. Group 1: Technical Indicators - The Relative Strength Index (RSI) is utilized to identify oversold stocks, with a reading below 30 indicating oversold conditions [2]. - XNCR's current RSI reading is 27.2, suggesting that the heavy selling pressure may be exhausting, indicating a possible price rebound [5]. Group 2: Fundamental Indicators - Analysts have raised earnings estimates for XNCR by 1.6% over the last 30 days, which typically correlates with price appreciation in the near term [6]. - XNCR holds a Zacks Rank 1 (Strong Buy), placing it in the top 5% of over 4,000 ranked stocks based on earnings estimate revisions and EPS surprises, further supporting the potential for a turnaround [7].

Group 1 - Xencor (XNCR) has experienced significant selling pressure, resulting in a 23.7% decline over the past four weeks, but it is now considered oversold, indicating potential for recovery as analysts expect improved earnings [1] - The Relative Strength Index (RSI) is a key technical indicator used to identify oversold stocks, with a reading below 30 typically indicating oversold conditions [2] - The RSI helps investors identify potential price reversals, suggesting that if a stock is undervalued due to excessive selling, it may present a buying opportunity [3] Group 2 - The RSI for XNCR is currently at 20.84, suggesting that the heavy selling may be nearing exhaustion and a trend reversal could occur soon [5] - Analysts have raised earnings estimates for XNCR, with a 1.6% increase in the consensus EPS estimate over the last 30 days, indicating potential price appreciation [6] - XNCR holds a Zacks Rank 1 (Strong Buy), placing it in the top 5% of over 4,000 ranked stocks based on earnings estimate revisions and EPS surprises, further supporting the likelihood of a turnaround [7]

Core Viewpoint - Xencor (XNCR) has been upgraded to a Zacks Rank 1 (Strong Buy), indicating a positive trend in earnings estimates which is a significant factor influencing stock prices [1][2]. Earnings Estimates and Stock Price Movement - The Zacks rating system is based on changes in earnings estimates, which are strongly correlated with near-term stock price movements [3][5]. - Institutional investors utilize earnings estimates to determine the fair value of stocks, leading to buying or selling actions that affect stock prices [3]. Company Performance and Outlook - The upgrade for Xencor reflects an improvement in the company's underlying business, suggesting that investor sentiment may drive the stock price higher [4]. - Xencor is projected to earn -$3.68 per share for the fiscal year ending December 2024, representing a year-over-year decline of 76.9% [7]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with Zacks Rank 1 stocks historically generating an average annual return of +25% since 1988 [6]. - Only the top 5% of Zacks-covered stocks receive a 'Strong Buy' rating, indicating superior earnings estimate revisions [8][9].

Financial Position - Xencor has a strong financial position with approximately $707 million in cash, cash equivalents, and marketable debt as of December 31, 2024[9]. Drug Development Pipeline - The company is advancing three novel T-cell engagers (TCEs) in Phase 1 studies focused on oncology, specifically targeting metastatic castration-resistant prostate cancer (mCRPC) and first-line non-small cell lung cancer (NSCLC)[7]. - XmAb942 (Xtend™ TL1A) is set to initiate studies in Q4 2024, while Plamotamab (CD20xCD3) is expected to enter Phase 1 in the first half of 2025[7]. - XmAb819 (ENPP3 x CD3) is currently in a Phase 1 dose escalation study for clear cell renal cell carcinoma (ccRCC), showing promising initial data with no maximum tolerated dose reached[21]. - XmAb541 (CLDN6 x CD3) is also in Phase 1, demonstrating high selectivity for CLDN6 over similar proteins, targeting ovarian and endometrial cancers[23]. - XmAb808 (B7-H3 x CD28) is in Phase 1, designed to enhance selective T cell activation in solid tumors, with ongoing patient enrollment[35]. - XmAb942 and XmAb TL1A x IL-23 are in development for ulcerative colitis, leveraging validated half-life extension technology[75]. - The first-in-human clinical study for XmAb942 is planned to initiate in Q4 2024[29]. - The initiation of Phase 1/2 study for Plamotamab (CD20 x CD3) in rheumatoid arthritis is set to begin[95]. - XmAb942 is expected to have single ascending dose (SAD) and multiple ascending dose (MAD) readouts in the immunology portfolio[95]. - XmAb717-04 and XmAb717-05 expansion readouts are anticipated in 1H 2025[93]. - The first-in-class potential for XmAb TL1A x IL-23 is being explored with a study planned for 2026[82]. Technology and Innovation - The company has a robust patent portfolio with over 1,600 patents issued and pending worldwide, enhancing its competitive edge in the market[7]. - Xencor's drug development strategy emphasizes rapid prototyping and strict evaluation of data to maximize outcomes for stakeholders[9]. - The company’s Xtend™ Fc technology has shown to significantly improve half-life and dosing frequency compared to traditional antibodies[77]. - XmAb942 utilizes Xtend™ Fc domain technology with a half-life of 23 days, supporting dosing every 8 to 12 weeks[29]. Collaborations and Market Strategy - The company is exploring technology licensing to expand its pipeline with minimal opportunity cost, indicating a strategic approach to market expansion[13]. - Xencor's collaborations with Johnson & Johnson focus on prostate cancer combinations, leveraging access to J&J's resources for enhanced development[34]. Market Opportunities - Current market for rheumatoid arthritis treatments exceeds $20 billion, with unmet needs for moderate-to-severe systemic lupus erythematosus (SLE) estimated at over $5 billion in the US[44]. - The global IBD drug market is projected to exceed $23 billion by 2030, highlighting significant unmet medical needs in inflammatory bowel disease[72]. - The bispecific antibody class is positioned to address significant limitations in current autoimmune disease treatments, with ongoing studies supporting its efficacy[43]. Clinical Outcomes - Vudalimab, a dual checkpoint inhibitor (PD-1 x CTLA-4), has shown a low rate of treatment discontinuation due to adverse events in ongoing studies[91]. - Vudalimab monotherapy has demonstrated clinical responses in 5 out of 12 evaluable patients with metastatic castration-resistant prostate cancer (mCRPC)[93]. - XmAb drug candidates are advancing with multiple dose expansions planned, including XmAb819 and XmAb808 in oncology[95]. - The company aims to evaluate the safety of Vudalimab in combination with chemotherapy for non-small cell lung cancer (NSCLC)[93]. - XmAb657, designed for autoimmune diseases, has demonstrated over 90% reduction in B-cell counts in both bone marrow and whole blood across dose cohorts[56]. - Plamotamab, a subcutaneous CD20 x CD3 bispecific antibody, is planned for Phase 1b/2a study initiation in the first half of 2025, focusing on rheumatoid arthritis[58].