Xencor, Inc. · NASDAQ:XNCR
Xencor — Investor Presentation (September 2026)
62 slides from Xencor's investor presentation, September 2026
Slide 1: Designing Proteins, Delivering Medicines: Corporate Overview
Designing Proteins Delivering Medicines ® Corporate Overview September 2026
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 re
Slide 3: Xencor clinical innovation cycle powered by XmAb engineering platforms
Xencor clinical innovation cycle powered by XmAb® engineering platforms Validated XmAb® R&D platforms enable Purpose-built molecules solve complex biological rapid, modular drug design engineering challenges for better drugs Xencor’s world-leading protein engineering capabilities Rapid prototyping a
Slide 4: Pipeline of next-gen T-cell engagers and novel antibodies
Our pipeline of next-gen T-cell engagers and novel antibodies is purpose-built with defined opportunities across oncology and autoimmune disease XmAb® Program Targets Indications Discovery Preclinical Phase 1 Phase 2 Phase 3 Platforms Solid Tumor Oncology: T-cell Engagers (CD3 & CD28) XmAb819 ENPP3
Slide 5: XmAb drug development model validated by commercialized medicines
XmAb® drug development model is validated by multiple commercialized medicines and pivotal- or late-stage programs XmAb® toolkits enable rapid Continued clinical success and commercialization of partner prototyping and lead optimization programs supports Xencor’s internal pipeline advancement XmAb®
Slide 6: Partner XmAb antibodies generate potential milestone and royalty revenues
Differentiated XmAb® antibodies developed by partners generate potential milestone and royalty revenues to offset internal development costs Potential Milestone Partner Program XmAb® Indications1 Status1 Royalty % Payments1 PNH, aHUS, Ultomiris® Xtend gMG, NMOSD Marketed Low SD2 All milestones paid
Slide 7: Key clinical readouts expected in 2026
Focused clinical execution is expected to deliver key clinical readouts in 2026 and advance programs with additional data in 2027 XmAb® Drug Candidate Indication 1H 2026 2H 2026 Oncology Portfolio Initiate tumor expansion cohorts Present RP3D monotherapy data XmAb819 ENPP3 x CD3 ccRCC for CRC, NSCLC
Slide 8: XmAb Bispecific T-Cell Engagers
XmAb® Bispecific T-Cell Engagers XmAb819 (ENPP3 x CD3) ® Phase 1 expansions and sub-studies in ENPP3-expressing tumors, including advanced ccRCC XmAb541 (CLDN6 x CD3) + XmAb808 (B7-H3 x CD28) Phase 1 in CLDN6+ HGSOC 8
Slide 9: ENPP3 x CD3 T-cell Engager in Development for ccRCC
XmAb819 (ENPP3 x CD3) ENPP3 x CD3 T-cell Engager in Development for ccRCC XmAb819 engages the Ectonucleotide pyrophosphatase / ENPP3 phosphodiesterase family member 3 XmAb® 2+1 immune system and activates T cells for highly potent and A differentially expressed target, with high Enables antibodies t
Slide 10: Opportunity for first-in-class T-cell engager in advanced ccRCC
XmAb819 (ENPP3 x CD3) Opportunity for a novel first-in-class T-cell engager to improve standard of care for patients with advanced ccRCC 3rd Line US ccRCC incidence 2nd Line ~ 60k1 new cases 1st Line ~ 10k addressable ~ 5k addressable per year ~ 20k addressable U.S. patients U.S. patients U.S. patie
Slide 11: Global RCC market expected to reach ~$12B in 2030
XmAb819 (ENPP3 x CD3) Size of global RCC market expected to reach ~$12B in 2030 with limited 2L+ treatment options beyond VEGF-TKI1 RCC U.S. Net Sales ($M)1,2 U.S. Total Addressable Market (TAM) in RCC in 2025 HIF2α inhibitor Checkpoint inhibitors VEGF-TKI 72% Aggregate U.S. Net Sales of Cabometyx®
Slide 12: Expansion opportunities for XmAb819 beyond ccRCC
XmAb819 (ENPP3 x CD3) Strategic expansion opportunities for XmAb819 beyond ccRCC ENPP3+ patients in 2L/3L+ setting1 of pRCC, CRC & NSCLC ~60K NSCLC Papillary RCC MSS Colorectal Cancer Adenocarcinoma Standard of care Standard of care Standard of care Cabozantinib Regorafenib or Fruquitinib Docetaxel
Slide 13: Phase 1 dose escalation: parallel IV and SC design
XmAb819 (ENPP3 x CD3) Phase 1 dose escalation: parallel IV and SC design Study Schema and Dosing Schedule High Dose Cohorts Key Eligibility Criteria Target Dose Range IV Cohort 11 • ≥ 18 years IV Cohort 10 • R/R ccRCC – prior CPI & VEGF TKI IV Cohort 9 SC Cohort 6 • Measurable disease by RECIST v1.1
Slide 14: Heavily pre-treated patient population in dose escalation
XmAb819 (ENPP3 x CD3) Heavily pre-treated patient population in ongoing dose escalation Baseline Characteristics Prior Therapy N 69 N 69 Median age, Years (Min, Max) 60 (34, 77) # Prior regimens, Median (Min, Max) 4 (1, 8) Male, n (%) 55 (80) 1, n (%) 5 (7) 2 16 (23) Race, n (%) 3 13 (19) White 61 (
Slide 15: AEs primarily during priming period and well managed
XmAb819 (ENPP3 x CD3) AEs primarily during the priming period and well managed with low overall rate at target doses Overall TEAE and Related TEAE >Day 29 to End of Study TEAE and Related TEAE by Maximum Severity Grade (N=69) by Maximum Severity Grade (N=69) • CRS profile is primarily low grade and
Slide 16: Clear evidence of dose response in dose escalation
XmAb819 (ENPP3 x CD3) Clear evidence of dose response in ongoing dose escalation of heavily pre-treated patients Best Percent Change from Baseline in Tumor Lesion (RECIST 1.1) Low Dose Cohorts (N=38)* Target Dose Cohorts (N=20)† ‡ * Excludes 4 patients without post-baseline scans and 3 patients with
Slide 17: Best overall response supports monotherapy development
XmAb819 (ENPP3 x CD3) Best overall response supports monotherapy development All responders treatment ongoing Percent Change from Baseline in Tumor Lesion Best Overall Response in the Efficacy Responders in Target Dose Range Evaluable Target Dose Range N 20* Objective Response Rate (ORR), % 25% (95%
Slide 18: Treatment has resulted in sustained disease control
XmAb819 (ENPP3 x CD3) 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. ENA2025, p
Slide 19: Preliminary efficacy demonstrates potential to advance standard of care
XmAb819 (ENPP3 x CD3) Preliminary efficacy demonstrates potential to advance standard of care for patients that have progressed after CPI and VEGF-TKI treatment Drug XmAb819 Belzutifan Belzutifan Tivozanib Preliminary Dose Phase 1 Dose IA1 & IA2 for Study TIVO-3 Study3 Escalation Expansion (ccRCC)1
Slide 20: Evolving ccRCC landscape and opportunity for XmAb819
XmAb819 (ENPP3 x CD3) Evolving ccRCC landscape has opportunity to redefine standard of care with XmAb819 in post IO and post VEGF-TKI treatment1-3 1L 2L+ Current IO + IO Landscape VEGF-TKI IO + VEGF-TKI HIF2α LITESPARK-011 Current Landscape Future Landscape VEGF-TKI HIF2α + IO + VEGF-TKI ± HIF-2α tr
Slide 21: XmAb819 on track for ccRCC pivotal study start in 2027
XmAb819 (ENPP3 x CD3) XmAb819 on-track for ccRCC pivotal study start planned for 2027 Presented initial dose-escalation data at AACR-NCI-EORTC 2025: Achieved 25% ORR in unselected, heavily pretreated ccRCC patients, meeting internal criteria for progression to dose-expansion phase; continued dose es
Slide 22: XmAb541 (CLDN6 x CD3) prioritized in combination with XmAb808
XmAb541 (CLDN6 x CD3) XmAb541 (CLDN6 x CD3) development has been prioritized in combination with XmAb808 (B7-H3 x CD28) XmAb541 engages the immune system and activates CLDN6 Claudin-6 T cells for highly potent and • Differential expression in cancerous tissue presents CLDN6 as an intriguing target t
Slide 23: XmAb541 + XmAb808 in ovarian cancer
XmAb541 (CLDN6 x CD3) XmAb808 (B7H3 x CD28) XmAb541 (CLDN6 x CD3) + XmAb808 (B7-H3 x CD28) in ovarian cancer XmAb541 activates T cells via Signal 1 provided by XmAb808 is designed to deliver tumor-targeted Signal 2, CD3 engagement CD28 co-stimulation, to complement Signal 1 anti-B7-H3 2 Fabs CLDN6 x
Slide 24: XmAb541 monotherapy data support XmAb541 + XmAb808
XmAb541 (CLDN6 x CD3) XmAb808 (B7H3 x CD28) XmAb541 monotherapy data support XmAb541 + XmAb808 Phase 1 dose-escalation study of XmAb541 XmAb541 Monotherapy Study Status • At the putative RP3D, emerging monotherapy data show clinical activity in heavily pretreated patients Monotherapy expansion cohor
Slide 25: XmAb CD28 bispecifics provide tumor-specific activation boost to CD3 bispecifics
XmAb541 (CLDN6 x CD3) XmAb808 (B7H3 x CD28) XmAb® CD28 bispecific antibodies provide a tumor-specific activation boost to CD3 bispecifics CLDN6 and B7H3 are XC53-251014: XmAb808 (B7H3 CLDN6 combo x CD28) w/808 enhances (PA-1, NSG-DKO) co-expressed in ovarian tumors activityofofGroup Baseline-correct
Slide 26: XmAb808 resists T-cell exhaustion and promotes durable killing
XmAb541 (CLDN6 x CD3) XmAb808 (B7H3 x CD28) XmAb808 resists T-cell exhaustion and promotes durable killing by XmAb541 in vitro Combination re-activates exhausted T cells Combination overcomes drug-induced resistance 15,000 Unstimulated T cells 15,000 Prestimulated T cells PBS PBS XmAb808 15,000 XmAb
Slide 27: Integrated pipeline of next generation precision immunotherapy
Integrated pipeline of next generation precision immunotherapy XmAb819 2025 2026 2027 Start of Pivotal Study as Regulatory Approval and Commercial Launch ENPP3 x CD3 PoC DE Data RP3D Monotherapy in Advanced ccRCC XmAb541 2025 2026 CLDN6 x CD3 PoC DE Data RP3D + XmAb808 2026 Start of combination stud
Slide 28: XmAb TL1A Pipeline
XmAb® TL1A Pipeline ® XmAb942 (Xtend TL1A) Ongoing Phase 2b in Ulcerative Colitis XmAb412 (TL1A x IL-23p19) Ongoing Phase 1 Study in Healthy Participants 28
Slide 29: Best-in-class TL1A candidates in large and growing IBD market
Xencor is positioned with best-in-class drug candidates targeting TL1A in large and growing market for biologic therapies to treat IBD Program Target 2025 Net Sales (All Indications)1 Global annual IBD spend $24.6b Top biologics indicated for treating moderately to severely active UC + CD by 20301 S
Slide 30: Over half of UC patients do not adequately respond to biologic therapy
More than half of patients with moderately to severely active UC do not adequately respond to biologic therapy Advanced therapy clinical remission rates in ulcerative colitis (placebo adjusted) 40% TL1A IL23 α4β7 JAK S1P miR-124 30% 28% 27% 26% 26% 24% 20% 21% 22% Bio-naïve 20% 15% 16% 13% 10% 0% Tu
Slide 31: TL1A clinical strategy aligned with future of IBD treatment
Xencor’s TL1A clinical strategy is aligned with the future of IBD treatment Current most prescribed Future IBD treatment landscape biologic therapy (Survey of gastroenterologists1) Oral Class 25% Current Landscape of surveyed gastroenterologists would Oral JAKi Bispecifics use a TL1AxIL23 bispecific
Slide 32: XmAb protein engineering enables differentiated treatment options for autoimmune disease
XmAb® protein engineering enables differentiated, potentially best-in-class treatment options for autoimmune and inflammatory diseases Design Objectives for a Novel Next-Gen Anti-TL1A Design Objectives for a Novel TL1A x IL-23p19 Bispecific anti-TL1A anti-TL1A anti-IL23 2 Fabs Class-leading potency
Slide 33: XmAb942 best-in-class anti-TL1A in rapidly expanding market
XmAb942 (TL1A) XmAb942 positioned as best-in-class anti-TL1A mAb in a rapidly expanding market targeting TL1A across autoimmune and inflammatory diseases TL1A Expected to be Cornerstone of Advanced Therapy in IBD & TAM Expanding to AID Broadly Multi-indication immune franchise opportunities Anti-TL1
Slide 34: XmAb942 best-in-class clinical profile versus 1st gen TL1A mAbs
XmAb942 (TL1A) XmAb942 exhibits best-in-class clinical profile versus 1st gen TL1A mAbs Class Leading Higher consistency of adequate drug exposure driven Drug Exposure by potency and low rates of immunogenicity Class Leading Clinical Convenience Single subcutaneous injection maintenance dose every 1
Slide 35: Phase 1 first-in-human study in healthy participants
XmAb942 (TL1A) The Phase 1 first-in-human study in healthy participants efficiently leveraged the known safety profile of the anti-TL1A class1 Single Ascending Dose (n=48) Study Design Elements • Randomized, double-blind, placebo-controlled A5 (n=8) A6 (n=8) • SAD (Part A) and MAD (Part B) cohorts A
Slide 36: XmAb942 is safe and well tolerated in healthy participants
XmAb942 (TL1A) XmAb942 is safe and well tolerated in healthy participants All treatment emergent adverse events (TEAEs) were mild or moderate. Rates of overall TEAEs were similar in XmAb942 and placebo: 75% (36/48 participants) vs. 69% (11/16 participants). There were no serious or severe TEAEs, and
Slide 37: XmAb942 extended exposure supports 12-week dosing interval
XmAb942 (TL1A) XmAb942 extended serum exposure and target engagement support the 12-week dosing interval during maintenance in XENITH-UC Drug Concentration Complexed Soluble TL1A Free Soluble TL1A (SAD) IV and SC Single Dose Multiple Dose (MAD) IV Dose-dependent and durable increases in Rapid and su
Slide 38: XmAb942 favorable immunogenicity profile versus 1st generation class
XmAb942 (TL1A) XmAb942 has a favorable immunogenicity profile compared to 1st generation anti-TL1A class Reported rate of NAb+ in healthy participants* Reported rate of ADA+ in healthy participants** 20% 100% 98% 15% 14% 75% 65% 57% 10% 50% 48% 6% 25% 5% 25% 2% 0% 0% NR 0% 3 XmAb942 XmAb942 Duvakitu
Slide 39: XENITH-UC Study: Phase 2b design
XmAb942 (TL1A) 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 d
Slide 40: Exposure-response across biologic targets in ulcerative colitis
XmAb942 (TL1A) Consistent relationship of exposure-response across biologic targets in ulcerative colitis studies is the pharmacological thesis for XENITH-UC Anti-TL1A Anti-α4β7 Anti-IL23 Afimkibart Vedolizumab Guselkumab Clinical remission exposure-response at Clinical remission exposure-response a
Slide 41: XmAb942 predicted to exceed 1st gen benchmarks of TL1A inhibition
XmAb942 (TL1A) XmAb942 is predicted by quantitative pharmacology model to exceed 1st gen benchmarks of TL1A target inhibition in XENITH-UC >99% TL1A Inhibition >90% TL1A Inhibition Molecule Induction (Week 12) Maintenance (Week 52) XmAb942 86% Q12W dosing 90% Afimkibart 40% Q4W 68% Tulisokibart 31%
Slide 42: XmAb942 predicted to maintain higher exposure with fewer injections
XmAb942 (TL1A) XmAb942 is predicted to maintain higher exposure compared to other TL1A antibodies during both induction and maintenance with fewer injections Model-predicted pharmacokinetics (PK) Model-predicted pharmacodynamics (PD) in tissue A unified quantitative systems pharmacology (QSP) model
Slide 43: Favorable XmAb942 clinical convenience in XENITH-UC
XmAb942 (TL1A) Favorable XmAb942 clinical convenience in XENITH-UC, with a significant reduction of injection burden in maintenance period Induction Maintenance Week 0 2 6 10 12 24 36 48 XmAb942 12 weeks 12 weeks 12 weeks XENITH-UC Week 0 2 6 10 12 16 20 24 28 32 36 40 44 48 52 Afimkibart AMETRINE-U
Slide 44: New XenLock bispecifics designed for convenience, efficacy and immunogenicity
XmAb412 (TL1A x IL23p19) New XenLock bispecifics are designed to meet the high bar for patient convenience, efficacy and immunogenicity in autoimmune disease Fabs optimized separately With XenLock Fab domains, XmAb412 (TL1A x IL23p19) is the Ultra-high affinity each pair of light and heavy first XmA
Slide 45: XmAb412 poised to be best-in-class biologic for IBD
XmAb412 (TL1A x IL23p19) XmAb412 poised to be best-in-class biologic for IBD and deliver PoC for new XenLock bispecific platform for autoimmune and inflammatory disease XmAb412 in healthy participants initiated enrollment in XenLock Fab Domains third quarter of 2026. anti-TL1A anti-IL23 XmAb412 demo
Slide 46: XmAb412 suppresses TL1A and IL23 with equal potency to monospecific mAbs
XmAb412 (TL1A x IL23p19) XmAb412 suppresses two important inflammatory axes – TL1A and IL23 with equal potency to best-in-class monospecific mAbs Requires half the antibody concentration as equivalent co-formulation doses αTL1A αIL23p19 XmAb412 inhibits TL1A-induced XmAb412 inhibits IL23 activity ap
Slide 47: Data support 60- to 70-day half-life in humans
XmAb412 (TL1A x IL23p19) Data support a 60- to 70-day half-life in humans, enabling a potential dosing interval of every 8 to 12 weeks or longer1 NHP half-life > 20 days Durable engagement in NHPs 10,000 1,000,000 100,000 XmAb412 (μg/mL) sTL1A (pg/mL) 1,000 10,000 1,000 Free sTL1A 100 Complexed sTL1
Slide 48: XmAb412 avoids large immune complex formation seen in 2+2 formats
XmAb412 (TL1A x IL23p19) XmAb412 avoids large immune complex formation seen in 2+2 formats, which reduces potential immunogenicity impact to clinical outcomes Possible Immune Complexes Antibodies Unbound 1+1 Format with TL1A Antibodies TL1A IL23 + + 1,000 2+2 Format Nomazlized A280 500 XmAb412 (1+1)
Slide 49: XmAb412 delivers dual targeted therapy without co-formulation complexity
XmAb412 (TL1A x IL23p19) XmAb412 is designed to deliver the promise of dual targeted therapy for IBD but avoid complex development of co-formulation approaches DUET-UC Study1 (Inadequate Response to ≥2 ST Classes) Comparison of IBD study sizes2 Co-formulation = 7 Large Component Studies Placebo 5% 7
Slide 50: TL1A development roadmap for XmAb942 and XmAb412
Xencor’s TL1A development roadmap integrates XmAb942 and XmAb412 decision points to define registration enabling studies in IBD 2025 2026 2027 2028+ XmAb942 Phase 1a Phase 2b 12 week 48 week XmAb942 Study TL1A HV Study Ulcerative Colitis Study PAS PAS Indication A Registration Enabling IBD Studies X
Slide 51: Next clinical development milestones for TL1A pipeline
Next clinical development milestones for Xencor’s TL1A pipeline Start of Phase 1 first-in-human study of XmAb412 YE26 Update on enrollment and blinded interim analysis of XENITH-UC 1H27 Interim results of the Phase 1 first-in-human study of XmAb412 2H27 12-week induction primary endpoint of XENITH-U
Slide 52: B-cell depleting bispecific antibodies in autoimmune disease
XmAb® Bispecific T-Cell Engagers ® B-cell depleting bispecific antibodies in autoimmune disease 52
Slide 53: XmAb TCEs can address unmet needs in autoimmune disease
XmAb® TCEs can address significant unmet needs for autoimmune disease responsive to targeted B-Cell depletion1 Deep B-cell depletion with T-cell engagers could help “reset” the immune system for patients with autoimmune disease ~4.5m patients in the U.S. by 2030 Cytotoxic perforins Hematology Neurol
Slide 54: Plamotamab is a subcutaneous CD20 x CD3 T-cell engager in Phase 1b
Plamotamab (CD20 x CD3) Plamotamab is a subcutaneous CD20 x CD3 T-cell engager in Phase 1b study Proof-of-concept for the T-cell engager class in autoimmune and inflammatory disease XmAb® CD20 x CD3 Bispecific Design Positioned for Success • Plamotamab designed in a • N=154 from dose escalation and
Slide 55: Durable B-cell depletion with single dose of plamotamab in NHPs
Plamotamab (CD20 x CD3) Durable B-cell depletion was observed in blood and lymphoid organs with a single dose of plamotamab in NHPs Blood B cells Bone marrow B cells Lymph node B cells 3 2.5 B cell / T cell (CD40+ / CD8+) B cell / T cell (CD40+ / CD8+) CD40+ B cells (vs baseline) 1.2 Low dose Low do
Slide 56: >95-99% peripheral B-cell depletion in lymphoma patients
Plamotamab (CD20 x CD3) >95-99% peripheral B-cell depletion was observed in lymphoma patients with IV & SC dosing in the Phase 1 monotherapy study Significant Reduction in B-cell Count Percent Reduction of B Cells in Bone Marrow Percent Reduction of B Cells in Whole Blood Flow Cytometry Within First
Slide 57: Phase 1b open-label study design in rheumatoid arthritis
Plamotamab (CD20 x CD3) Ongoing Phase 1b open-label study design in rheumatoid arthritis (RA) Part A - Single Dose SAD Part B - Priming, Target Dose SAD Highly efficient study design leverages Priming Dose Exploration Target Dose Exploration known oncology exposure profile A3 B3 Population A2 Prime
Slide 58: XmAb657 is a CD19 x CD3 T-cell engager for autoimmune disease
XmAb657 (CD19 x CD3) XmAb657 is a CD19 x CD3 T-cell engager optimized for autoimmune disease Rational XmAb® Design Positioned for Success • High affinity and stability anti-CD19 NHP studies have shown effective binder B-cell depletion with single dose anti-CD19 2 Fabs • Bivalent to efficiently targe
Slide 59: Deep B-cell depletion sustained for at least 28 days in NHPs
XmAb657 (CD19 x CD3) Deep B-cell depletion was sustained for at least 28 days with a single dose in NHPs Peripheral blood Bone marrow Lymph nodes 10000 3 5 % B cells among bone % B cells among lymph marrow leukocytes B cells/μL of blood XmAb 657 5000 node leukocytes 4 2 100 3 Single IV 80 60 2 Dose
Slide 60: XmAb657 rationally designed for autoimmune disease; Phase 1 initiated Q4 2025
XmAb657 (CD19 x CD3) XmAb657 is rationally designed for autoimmune disease, and a Phase 1 study was initiated in Q4 2025 XmAb657 serum conc. [ng/mL], log scale • Has been observed to demonstrate Long half life with deep and durable B-cell depletion in Xtend Fc technology NHPs, enabled by potentially
Slide 61: Phase 1 open-label hybrid design of HV and AID patients
XmAb657 (CD19 x CD3) Phase 1 open-label study hybrid design of HV and AID patients Part A - Single Dose SAD Part B - Priming, Target Dose SAD Population Priming Dose Exploration Target Dose Exploration • Healthy volunteers (HV) and autoimmune A3 B3 diseases (AID): idiopathic inflammatory myopathies
Slide 62: Key clinical readouts expected in 2026 and 2027
Focused clinical execution is expected to deliver key clinical readouts in 2026 and advance programs with additional data in 2027 XmAb® Drug Candidate Indication 1H 2026 2H 2026 Oncology Portfolio Initiate tumor expansion cohorts Present RP3D monotherapy data XmAb819 ENPP3 x CD3 ccRCC for CRC, NSCLC