Slide 1: Initial Results from Ongoing Dose-Escalation Study of XmAb819 & Oncology Pipeline Update
® Initial Results from Ongoing Dose-Escalation Study of XmAb819 & Oncology Pipeline Update October 24, 2025
Slide 2: Today's Speakers
2 Today’s Speakers Bassil Dahiyat, Ph.D. President & Chief Executive Officer Xencor Management Guest Speaker Sumanta Pal, M.D., F.A.S.C.O. Professor, Department of Medical Oncology & Therapeutics Research Co-director, Kidney Cancer Program City of Hope Comprehensive Cancer Center Dane Leone Executiv
Slide 3: Today's Agenda
3 Initial Results from Ongoing Dose-Escalation Study of XmAb819 (ENPP3 x CD3) in Advanced Clear Cell Renal Cell Carcinoma Summary and Q&A Overview & Xencor’s Oncology Portfolio Today’s Agenda Competitive Position and Commercial Opportunity for XmAb819 Early Look at XmAb514 (CLDN6 x CD3) in Advanced
Slide 4: Forward-Looking Statements
4 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
Slide 5: Proven Power of XmAb Engineering: Proteins By Design
5 • XmAb Fc Domains augment native immune functions in molecules and/or control their structure, while preserving desired attributes • XmAb engineered antibodies are designed to solve complex biologic problems • Strong patent portfolio Oncology: Advancing a portfolio novel TCEs • XmAb819 (ENPP3xCD3)
Slide 6: Next-Gen XmAb Drug Design in Oncology & Autoimmune Diseases
6 Program Targets XmAb® Platforms Indications Discovery Preclinical Phase 1 Phase 2 Phase 3 Solid Tumor Oncology: T-cell Engagers (CD3 & CD28) XmAb819 ENPP3 x CD3 2+1 Bispecific ccRCC XmAb541 CLDN6 x CD3 2+1 Bispecific, Xtend Ovarian cancer, GCT, oncology XmAb808 B7-H3 x CD28 2+1 Bispecific, Xtend P
Slide 7: XmAb819: ENPP3 x CD3 T-cell Engager in Development for ccRCC
7 XmAb819: ENPP3 x CD3 T-cell Engager in Development for ccRCC A differentially expressed target, with high level expression in renal cell carcinoma and low-level expression on normal tissues1 Bispecific Fc Domain anti-ENPP3 2 Fabs anti-CD3 1 scFv High ENPP3 Low ENPP3 Selective T-cell directed cytot
Slide 8: 2+1 Bispecifics: XmAb T Cell Engagers Use Multiple Formats and Affinity Designs
8 2+1 Bispecifics: XmAb® T Cell Engagers Use Multiple Formats and Affinity Designs to Customize for Each Tumor Target -1 0 1 2 3 4 5 0 20 40 60 Log10 [Concentration (pM)] R T C C A c ti v it y ( % ) High density Low density EC50 = 9.4 pM EC50 > 10 5 pM Low expressing normal cell High expressing tumo
Slide 9: Ongoing Phase 1 Dose-Escalation of XmAb819 in ccRCC Initial Results
9 ® Ongoing Phase 1 Dose-Escalation of XmAb819 in ccRCC Initial Results Data Cut-off: September 19, 2025
Slide 10: XmAb819 Phase 1 Dose Escalation: Parallel IV and SC Design
10 TD Target Dose CPI checkpoint inhibitor Key Eligibility Criteria • ≥ 18 years • R/R ccRCC – prior CPI & VEGF TKI • Measurable disease by RECIST v1.1 • No prior anti-ENPP3 therapy Objectives • Safety and tolerability • Identify recommended dose • Pharmacokinetics • Anti-tumor activity XmAb819 Phas
Slide 11: Pharmacokinetic Profile of XmAb819 Supports QW - Q2W Dosing
11 Steady state drug concentrations attained in Cohorts 9 and 10 fall within the PK target dose range expected to achieve anti-tumor activity Pharmacokinetic Profile of XmAb819 Supports QW - Q2W Dosing Parameter Value Half-life 8.7 Days Subcutaneous Administration Tmax 5.5 Days Absolute Bioavailabi
Slide 12: Heavily Pre-treated Patient Population in Ongoing Dose Escalation
12 Heavily Pre-treated Patient Population in Ongoing Dose Escalation Baseline Characteristics N 69 Median age, Years (Min, Max) 60 (34, 77) Male, n (%) 55 (80) Race, n (%) White Other 61 (88) 8 (12) Time since initial diagnosis, Months (Min, Max) 53.6 (8, 259) IDMC risk score at initial diagnosis, n
Slide 13: Low Rate of Discontinuations Due to Adverse Events
13 Low Rate of Discontinuations Due to Adverse Events Patient Disposition N 69 Treatment Status, n (%) Ongoing Discontinued 17 (25) 52 (75) Reason for Treatment Discontinuation, n (%) Adverse event* Physician decision Subject declines further treatment Progressive disease Clinical progression 3 (4)
Slide 14: Safety Summary – Well-tolerated Treatment
14 Safety Summary – Well-tolerated Treatment With >90% of Patients Reaching Target Dose; Low Rate of Discontinuation Treatment Emergent Adverse Events (TEAE), n (%) N 68 (99) Grade ≥3 48 (70) Related Grade ≥3 31 (45) Serious TEAE 35 (51) Related Serious TEAE 28 (41) Lead to Dose Reduction 4 (6) Did
Slide 15: CRS Profile Primarily Low Grade and Occurs in Initial Priming Doses
15 CRS Profile Primarily Low Grade and Occurs in Initial Priming Doses Correct dose preparation resulted in 4% Grade 3 CRS (2/51), whereas dose preparation errors resulted in 28% Grade 3 CRS (5/18) In the target dose range, correct dose preparation resulted in 6% Grade 3 CRS (1/18), whereas dose pre
Slide 16: AEs Primarily During the Priming Period and Well Managed
16 AEs Primarily During the Priming Period and Well Managed With Low Overall Rate at Target Doses Overall TEAE and Related TEAE by Maximum Severity Grade (N=69) >Day 29 to End of Study TEAE and Related TEAE by Maximum Severity Grade (N=69) Most common AEs are CRS and rash • Majority of CRS events ar
Slide 17: Clear Evidence of XmAb819 Dose Response in Heavily Pre-Treated Patients
17 Clear Evidence of XmAb819 Dose Response in Ongoing Dose Escalation of Heavily Pre-Treated Patients Best Percent Change from Baseline in Tumor Lesion (RECIST 1.1) Target Dose Cohorts (N=20)†Low Dose Cohorts (N=38)* * Excludes 4 patients without post-baseline scans and 3 patients with non-evaluable
Slide 18: Best Overall Response Supports Monotherapy Development
18 Best Overall Response Supports Monotherapy Development All Responders Treatment Ongoing Percent Change from Baseline in Tumor Lesion Responders in Target Dose RangeBest Overall Response in the Efficacy Evaluable Target Dose Range N 20* Objective Response Rate (ORR), % (95% CI) 25% (9, 49) Complet
Slide 19: Majority of Patients Experience Reduction in Tumor Lesions
19 Majority of Patients Experience Reduction in Tumor Lesions Percent Change from Baseline, Target Dose Range (N=20) Excludes 3 patients without post-baseline scans and 1 patient with non-evaluable post-baseline measurements
Slide 20: XmAb819 Treatment Has Resulted in Sustained Disease Control
20 XmAb819 Treatment Has Resulted in Sustained Disease Control Response by Subject, Efficacy Evaluable (RECIST 1.1) Target Dose Range (N=20) † PD at first scan (D48) prior to receiving target dose on D50. Continued treatment post-progression resulted in a 47% tumor reduction. †
Slide 21: Sumanta (Monty) Kumar Pal, M.D., F.A.S.C.O.
21 Sumanta (Monty) Kumar Pal, M.D., F.A.S.C.O., is an internationally recognized leader in kidney cancer. Dr. Pal maintains one of the largest portfolios of clinical trials for kidney cancer on the West Coast. He developed an integrated program that focuses heavily on collaborations with basic scien
Slide 22: Case Example: ~63% Target Lesion Reduction Despite Membrane TPS<25%
22 Case Example: ~63% Target Lesion Reduction Despite Membrane TPS<25% Indicates Potential Bystander Effect • 56-year-old male diagnosed ~10 years ago; metastatic disease less than 5 years ago • 2 prior lines of therapy: cabozantinib/nivolumab (1 month), lenvatinib/everolimus (3 years) Decrease in t
Slide 23: Competitive Positioning & Commercial Opportunity
23 ® Competitive Positioning & Commercial Opportunity
Slide 24: XmAb819 On-track for ccRCC Pivotal Study Start
24 XmAb819 On-track for ccRCC Pivotal Study Start During 2027 Achieved 25% ORR in unselected, heavily pretreated ccRCC patients, meeting internal criteria for progression to dose-expansion phase Well-tolerated safety profile observed with mainly Grade 1/2 CRS, transient rash and liver enzyme elevati
Slide 25: Size of Global RCC Market Expected to Reach ~$12B in 2030
25 Size of Global RCC Market Expected to Reach ~$12B in 2030 With Limited 2L+ Treatment Options Beyond VEGF-TKI1 1 GlobalData 2 Company earnings reports Registered trademarks: Cabometyx (Exelixis, Inc.), Lenvima (Eisai R&D Management Co., Ltd.), Keytruda & Welireg (Merck Sharp & Dohme LLC), Opdivo (
Slide 26: Opportunity for a Novel First-in-class T-cell Engager in Advanced ccRCC
26 Opportunity for a Novel First-in-class T-cell Engager to Improve SoC for Patients With Advanced ccRCC ~ 20k addressable U.S. patients ~ 10k addressable U.S. patients ~ 5k addressable U.S. patients VEGF-TKI HIF2α inhibitor post IO + VEGF-TKI (LITESPARK-005) US ccRCC incidence ~ 60k1 new cases per
Slide 27: Evolving ccRCC Landscape Has Opportunity to Redefine SoC with XmAb819
27 Evolving ccRCC Landscape Has Opportunity to Redefine SoC with XmAb819 in 2L+ Post IO and VEGF-TKI Treatment VEGF-TKIIO + IO 1L 2L+ Today’s Landscape Tomorrow’s Landscape IO + VEGF-TKI HIF2α LITESPARK-012 VEGF-TKI ± HIF-2α IO + IO IO + VEGF-TKI ± HIF-2α XmAb819 LITESPARK-011 1 Choueiri, et al. Nat
Slide 28: XmAb819 Preliminary Efficacy Demonstrates Potential to Advance SoC
28 XmAb819 Preliminary Efficacy Demonstrates Potential to Advance SoC for Patients That Have Progressed After CPI and VEGF-TKI Treatment Drug XmAb819 Belzutifan Belzutifan Tivozanib Study Preliminary Dose Escalation Phase 1 Dose Expansion (ccRCC)1 IA1 & IA2 for LITESPARK-0052 TIVO-3 Study3 Efficacy
Slide 29: Strategic Expansion Opportunities for XmAb819 Beyond ccRCC
29 Standard of care Cabozantinib Standard of care Regorafenib or Fruquitinib or FTD/TPI + Bevacizumab Standard of care Docetaxel 1 Estimates for U.S. 2025 ENPP3 population based upon H-Score of ≥1 ~60K Papillary RCC NSCLC Adenocarcinoma MSS Colorectal Cancer ENPP3+ patients in 2L/3L+ setting1 of pRC
Slide 30: Early Look at XmAb541 in Advanced Ovarian Cancer, Endometrial Cancer and Germ Cell Tumors
30 ®Early Look at XmAb541 in Advanced Ovarian Cancer, Endometrial Cancer and Germ Cell Tumors
Slide 31: XmAb541: CD3 T-cell Engager for Ovarian Cancer & Solid Tumors
31 XmAb®541: CD3 T-cell Engager for Ovarian Cancer & Solid Tumors XmAb541 (CLDN6 x CD3) Phase 1 Dose Escalation StudyXmAb 2+1 Design Highly selective for CLDN6 over CLDN9 • Differential expression in cancerous tissue presents CLDN6 as an intriguing target • CLDN family members, which are small membr
Slide 32: XmAb541 Best Overall Response at Most Recently Evaluated IV Dose Level
32 -100% -80% -60% -40% -20% 0% 20% 40% 60% B e s t % C h a n g e f ro m B a s e lin e XmAb541 Best Overall Response at Most Recently Evaluated IV Dose Level PR SD PD Includes patients with CLDN6 tumor cell positivity ≥ 30% GCT Ova/Per GCT GCTOva GCT GCTEndOva Data cut-off: October 1, 2025 Ova ovari
Slide 33: Market Opportunity for XmAb541 in CLDN6+ Gynecological Tumors
33 Commercial OpportunitySoC Per Line of TherapyEpidemiology Ovarian Cancer Endometrial Cancer Germ Cell Tumors Total sales in 1H25: $338 million2 Platinum-based chemo Total sales in 1H25: $196 million2 Market Opportunity for Xmab541 in CLDN6+ Gynecological Tumors Approved drugs CLDN6 positivity: ~5
Slide 34: Closing Remarks
34 ® Closing Remarks
Slide 35: Building a Fully Integrated Oncology Company on Novel TCEs
35 Building a Fully Integrated Oncology Company on Novel TCEs XmAb819 2025 XmAb541 2035+2030 xCD3 Partnered Program (Amgen, MSD - HSD Royalty) xCD3 Partnered Program (Astellas, HSD - Low DD Royalty) xCD28 Partnered Program (Janssen, HSD - Low DD Royalty) Undisclosed TCE TCE Partnerships are Potentia
Slide 36: Q&A
36 ® Q&A
Slide 37: Initial Results from Ongoing Dose-Escalation Study of XmAb819 & Oncology Pipeline Update
® Initial Results from Ongoing Dose-Escalation Study of XmAb819 & Oncology Pipeline Update October 24, 2025