Slide 1: Interim Results from First-in-Human Study of XmAb942 & TL1A Pipeline Update
Interim Results from First-in-Human Study ® of XmAb942 & TL1A Pipeline Update April 29, 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements Certain statements contained in this presentation, other than statements of historical fact, may constitute forward- looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements r
Slide 3: Proven Power of XmAb Engineering: Proteins By Design
Proven Power of XmAb® Engineering: Proteins By Design® Small changes, Advancing an optimized portfolio Partnerships leverage big functional impacts of XmAb drug candidates modular XmAb technology • XmAb Fc Domains augment native immune • Oncology: 2 novel CD3 TCEs advancing in • More than 15 technol
Slide 4: Next-Gen XmAb Drug Design in Oncology & Autoimmune Diseases
Next-Gen XmAb® Drug Design in Oncology & Autoimmune Diseases Pipeline focus on T-cell engagers and bispecific mechanisms XmAb® Program Targets Indications Discovery Preclinical Phase 1 Phase 2 Phase 3 Platforms Solid Tumor Oncology: T-cell Engagers (CD3 & CD28) XmAb819 ENPP3 x CD3 2+1 Bispecific ccR
Slide 5: Potential Inflection Points for Xencor's Clinical Portfolio in 2025
Potential Inflection Points for Xencor’s Clinical Portfolio in 2025 XmAb Drug Candidate Indication 1H’25 2H’25 Oncology Portfolio Present initial Phase 1 data XmAb819 ENPP3 x CD3 ccRCC at a medical meeting CLDN6+ tumor types, XmAb541 CLDN6 x CD3 Characterization of target dose levels including ovari
Slide 6: IBD Remains a Significant Opportunity for Novel Therapy
IBD Remains a Significant Opportunity for Novel Therapy Chronic High-Burden Disease Current Standards of Care +3.3m Estimated Severe Symptoms diagnoses in • Diarrhea and rectal bleeding JAK S1P the U.S. and inhibitor modulator EU51 • Fever and fatigue ✓ Abdominal pain • Reduced appetite and weight l
Slide 7: TL1A Has Emerged As a Critical Node in IBD Pathophysiology
TL1A Has Emerged As a Critical Node in IBD Pathophysiology DC Endothelial Th1 Macrophage IFNγ, TNFα Crohn’s disease TL1A is expressed primarily by monocytes, Plasma cell Lymphocyte Rheumatoid arthritis macrophages, and dendritic cells. Helminthic infections ILC2 Fibroblast Th17 Psoriasis Allergic lu
Slide 8: XmAb Protein Engineering for Differentiated Treatment Options for IBD
XmAb® Protein Engineering for Differentiated, Potentially Best-in-Class Treatment Options for IBD XmAb942 Design for a Novel Next-Gen Anti-TL1A XENP53*** Design for TL1A x IL-23p19 Bispecific anti-TL1A Objectives Objectives 2 Fabs anti-TL1A anti-IL23 • Class-leading potency • Highly stable monovalen
Slide 9: XmAb942: Novel High-Affinity Anti-TL1A mAb Designed for Extended Half-Life
XmAb942: Novel High-Affinity Anti-TL1A mAb Designed for Extended Half-Life, Under Development for the Treatment of IBD Class Leading Target Inhibition XmAb942 utilizes Xtend Fc domain technology with potentially class- leading target neutralization Class Leading Clinical Convenience High concentrati
Slide 10: XmAb942 Phase 1 Study in Healthy Volunteers Interim Results
XmAb942 Phase 1 Study in Healthy Volunteers ® Interim Results 10
Slide 11: Interim Results From Phase 1 Study
Interim Results From Phase 1 Study Single Ascending Dose Highly efficient study design leverages 6 active:2 placebo per cohort known safety profile of anti-TL1A class A5 A6 Study Design Elements A3 A4 SC IV High High • Double-blind, placebo-controlled, first-in-human A1 A2 SC IV x1 dose x1 dose • SA
Slide 12: Baseline Characteristics
Baseline Characteristics Single Dose Multiple Dose Blinded Interim Data Cohort A1 Cohort A2 Cohort A3 Cohort A4 Cohort A5 Cohort A6 Cohort B1 Cohort B2 (XmAb942 + Placebo) SC, Low IV, Low SC, Med IV, Med SC, High IV, High IV, Low IV, Med N 8 8 8 8 8 8 8 8 Age in years (Mean, SD) 39, 9 32.5, 6 39.7,
Slide 13: Blinded Interim Safety Analysis from Healthy Volunteers In-Line With Expectations
Blinded Interim Safety Analysis from Healthy Volunteers In-Line With Expectations for Anti-TL1A Class Single Dose Multiple Dose Blinded Interim Data Cohort A1 Cohort A2 Cohort A3 Cohort A4 Cohort A5 Cohort A6 Cohort B1 Cohort B2 (XmAb942 + Placebo) SC, Low IV, Low SC, Med IV, Med SC, High IV, High I
Slide 14: XmAb942 Has Prolonged Serum Exposure in Humans
XmAb942 Has Prolonged Serum Exposure in Humans • Estimated terminal half-life is +71 days from pooled analysis of single-dose cohorts • No apparent impact of ADA on PK profile up to 16 weeks after single dose or 10 weeks after multiple Q4W dosing • Early multiple dose PK data consistent with single
Slide 15: XmAb942 Increases Total TL1A as Expected With Long Durability
XmAb942 Increases Total TL1A as Expected With Long Durability • Dose-dependent and durable increases in total TL1A , at least 16 weeks after a single dose of XmAb942, are consistent with high binding potency and extended serum exposure • Interim results support lower frequency of dosing compared to
Slide 16: Free sTL1A in Serum Drops and Stays Below Quantitative Thresholds
Free sTL1A in Serum Drops and Stays Below Quantitative Thresholds in Healthy Participants for At Least 16 Weeks Mean Free sTL1A Concentration vs. Nominal Time (SAD IV & SC) • All IV and SC dose levels had rapid and sustained reduction of free sTL1A below LLOQ for at least 16 weeks from a single dose
Slide 17: XmAb942 Model Predicts Sustained Effective Suppression of TL1A in the Gut
XmAb942 Model Predicts Sustained Effective Suppression of TL1A in the Gut in the Planned Phase 2 Dose Regimen • Phase 2 program is designed to maximize potential for greater efficacy than other anti-TL1A drugs in the clinic • Model predicts >90-95% inhibition at the lowest Phase 2 dose, >98-99% inhi
Slide 18: Interim SAD/MAD Data for XmAb942 Support Key Objectives
Interim SAD/MAD Data for XmAb942 Support Key Objectives for a Potential Best-in-Class Anti-TL1A Antibody Higher consistency of adequate drug exposure for better clinical outcomes in both induction and maintenance Single subcutaneous injection maintenance dose Maintenance period dosing every 12 weeks
Slide 19: XmAb942 Phase 2 Study in Ulcerative Colitis
XmAb942 Phase 2 Study ® in Ulcerative Colitis 19
Slide 20: XmAb942 Clinical Development Plan – XENITH
XmAb942 Clinical Development Plan – XENITH Phase 1a Phase 2b Phase 3 Healthy Participants Ulcerative Colitis Ulcerative Colitis Phase 1/2b Phase 2b/3 Crohn’s Disease Phase 2a Fibrostenotic Crohn’s Disease Atopic Dermatitis Expansion Primary Biliary Cholangitis Opportunities Primary Sclerosing Cholan
Slide 21: XmAb942 Predicted to Maintain Higher Exposure Than Tulisokibart
XmAb942 Predicted to Maintain Higher Exposure Than Tulisokibart at Phase 2 Target Dose Levels During Both Induction and Maintenance XmAb942 Target Phase 2 dose level Q12W at 12 - 52 weeks Tulisokibart 1000 mg IV at 0 weeks 500 mg IV at 2, 6 and 10 weeks 240 mg SC at 12 - 52 weeks (Q4W) 21
Slide 22: XENITH-UC Study: Phase 2b Design
XENITH-UC Study: Phase 2b Design Induction Maintenance Study Design Elements (12 weeks) (40 weeks) • Double-blind, placebo-controlled High dose IV • IV administration in induction N= ~67 • SC administration in maintenance Randomization 4:3:3:3 Medium dose IV Population N= ~51 Medium dose SC • Modera
Slide 23: Summary of XENITH Program Strategy
Summary of XENITH Program Strategy • Well-powered with achievable enrollment goals to support differentiated clinical outcomes • Thorough Phase 2 dose characterization supports efficient pivotal design • Rational program gating to XENITH expansion into Crohn’s disease and other disease indications b
Slide 24: TL1A x IL23p19 Lead Candidate Update
TL1A x IL23p19 ® Lead Candidate Update 24
Slide 25: XmAb TL1A x IL23p19 Bispecific Leads Have Competitive Functional Potency
XmAb TL1A x IL23p19 Bispecific Leads Have Competitive Functional Potency for TL1A and IL23 Inhibition DR3-mediated apoptosis IL23 reporter assay αTL1A αIL23 40,000 6 30,000 Xencor TL1a x IL23 XENP53*** Fold Change Risankizumab Risankizumab RLU Mirikizumab Mirikizumab 20,000 Guselkumab Guselkumab 3 X
Slide 26: XmAb942 Potential to Address Unmet Needs in Current Care for Patients With IBD
XmAb942 Potential to Address ® Unmet Needs in Current Care for Patients With IBD 26
Slide 27: Survey of Gastroenterologists Supports High Expected Utilization of Anti-TL1A Class
Survey of Gastroenterologists1 Supports High Expected Utilization of Anti-TL1A Class for IBD Treatment in the United States (>$17bn Market by 2030E2) ~9 out of 10 gastroenterologists surveyed expect Anti-TL1A class could capture ~1/3 of total market to use anti-TL1A drugs as the first or second line
Slide 28: Opportunity for Next-Gen Best-in-Class Anti-TL1A XmAb942 to Differentiate
Opportunity for Next-Gen Best-in-Class Anti-TL1A Xmab942 to Differentiate on What Matters Most to Clinicians and Patients1 Drug Exposure Matters Injection Burden Matters Dosing Frequency Matters >70% of gastroenterologists >80% of gastroenterologists >90% of gastroenterologists surveyed recognize th
Slide 29: Future of Anti-TL1As in IBD Is Combination With Current SOC Therapy & Dual MoAs
Future of Anti-TL1As in IBD Is Combination With Current SOC Therapy & Dual MoAs With Bispecifics (e.g., TL1A x IL23p19) CLINICAL RATIONALE COMMERCIAL STRATEGY PHYSICIANS’ SENTIMENT2 Synergistic potential with established Bispecifics leverage existing biologic ~90% of gastroenterologists surveyed tar
Slide 30: Xencor's Roadmap for Innovation in IBD and TL1A Program Expansion
Xencor’s Roadmap for Innovation in IBD and TL1A Program Expansion XmAb942 XENITH-UC readout XmAb942 Potential indication XmAb TL1A x IL23 expansion Phase 2 study start(s) XmAb942 Interim SAD & MAD data XmAb TL1A x IL23 with expected First-in-human study XENITH-UC study start initiation 2027+ XmAb942
Slide 31: Xencor Programs Targeting TL1A Have Achieved Key Milestones
Xencor Programs Targeting TL1A Have Achieved Key Milestones XmAb942 interim SAD/MAD results support the thesis of delivering effective drug exposure with convenient maintenance dosing TL1A and IL23p19 binder potency used for XENP53*** program supports effective bispecific target engagement XmAb942 a
Slide 32: Interim Results from First-in-Human Study of XmAb942 & TL1A Pipeline Update
Interim Results from First-in-Human Study ® of XmAb942 & TL1A Pipeline Update April 29, 2025