Slide 1: Results from Phase 1 Study of XmAb942 & TL1A Pipeline Update
Designing Proteins Delivering Medicines ® Results from Phase 1 Study of XmAb942 & TL1A Pipeline Update May 5, 2026
Slide 2: Today's Speakers
Today’s Speakers Xencor Management Guest Speaker Bassil Dahiyat, Ph.D. President & Chief Executive Officer Vipul Jairath, MBChB, Dphil, MRCP, FRCPC Professor of Medicine, Division of Gastroenterology Western University, Ontario, Canada Chief Medical Officer, Alimentiv John Desjarlais, Ph.D. Executiv
Slide 3: Today's Agenda
Today’s Agenda Overview & Xencor’s TL1A Portfolio Preclinical Characterization of XmAb412 & XenLock Platform XmAb942 Phase 1 Study in Healthy Participants: Final Results XENITH-UC: Global Phase 2b Study of XmAb942 TL1A Clinical Strategy & Development Roadmap Q&A Session 3
Slide 4: 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 5: Overview & Xencor's TL1A Portfolio
Overview & Xencor’s TL1A Portfolio ® Bassil Dahiyat, Ph.D. President & Chief Executive Officer 5
Slide 6: 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 7: XmAb drug development model validated by commercialized medicines and late-stage programs
XmAb® drug development model is validated by multiple commercialized medicines and pivotal- or late-stage programs XmAb® toolkits enable rapid prototyping Continued clinical success and commercialization of partner and lead optimization programs supports Xencor’s internal pipeline advancement XmAb®
Slide 8: Our 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 9: Focused clinical execution expected to deliver key readouts 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’26 2H’26 Oncology Portfolio Initiate tumor expansion cohorts Present RP3D monotherapy data XmAb819 ENPP3 x CD3 ccRCC for CRC, NSCLC and
Slide 10: Xencor positioned with best-in-class drugs targeting TL1A in large IBD market
Xencor positioned with best-in-class drugs 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 Skyrizi® (risa
Slide 11: XmAb protein engineering enables differentiated treatment options
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 12: XmAb942 positioned as best in class anti-TL1A mAb in expanding market
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-TL1A class could c
Slide 13: XmAb412 designed to deliver dual targeted therapy for IBD
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% 750 6 693 5 572 Golimumab
Slide 14: Preclinical Characterization of XmAb412 & XenLock Platform
Preclinical Characterization of XmAb412 & XenLock Platform ® John Desjarlais, Ph.D. EVP & Chief Scientific Officer 14
Slide 15: New XenLock bispecifics designed for patient convenience, efficacy and immunogenicity
New XenLock bispecifics 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 XmAb® bispecific engineered with
Slide 16: XmAb412 suppresses two important inflammatory axes – TL1A and IL23
XmAb412 suppresses two important inflammatory axes – TL1A and IL23 αTL1A αIL23p19 XmAb412 inhibits TL1A-induced XmAb412 inhibits IL23 activity apoptosis similar to a first-generation more potently than marketed monospecific anti-TL1A antibody monospecific IL23 antibodies 4 6 RLU (× 10,000) 3 (vs no
Slide 17: XmAb412 avoids large immune complex formation seen in 2+2 formats
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) + TL1A 2+2 + TL1A TL1A I
Slide 18: Data support a 60- to 70-day half-life in humans
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 sTL1A 100 10 10 0 7 14 21 28
Slide 19: XmAb412 poised to be best-in-class biologic for IBD
XmAb412 poised to be best-in-class biologic for IBD and deliver PoC for new XenLock bispecific platform for autoimmune and inflammatory disease Dosing of XmAb412 in healthy participants is expected to 3Q26 begin in the third quarter of 2026. XenLock Fab Domains anti-TL1A anti-IL23 XmAb412 demonstrat
Slide 20: XmAb942 Phase 1 Study in Healthy Participants Final Results
XmAb942 Phase 1 Study in Healthy Participants Final Results ® Mark Osterman, M.D., M.S.C.E SVP & Head of Clinical Development (Autoimmune) 20
Slide 21: Phase 1 first-in-human study in healthy participants
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 A3 (n=8) A4 (n=8
Slide 22: XmAb942 is safe and well tolerated in healthy participants
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 no TEAEs led t
Slide 23: XmAb942 has extended serum exposure in humans
XmAb942 has an extended serum exposure in humans and supports the 12-week dosing interval during maintenance in XENITH-UC Drug Concentration Drug Concentration Single Dose (SAD) IV and SC Multiple Dose (MAD) IV XmAb942 (μg/mL) XmAb942 (μg/mL) Low dose Low dose Medium dose Medium dose High dose Weeks
Slide 24: XmAb942 increases complexed total TL1A with extended durability
XmAb942 increases complexed total TL1A with extended durability Complexed Soluble TL1A Complexed Soluble TL1A Single Dose (SAD) IV and SC Multiple Dose (MAD) IV Complexed sTL1A (pg/mL) Complexed sTL1A (pg/mL) Placebo Placebo Low dose Low dose Medium dose Medium dose High dose Weeks Weeks Dose-depend
Slide 25: XmAb942 rapidly decreases free sTL1A below quantitative thresholds
XmAb942 rapidly decreases free sTL1A in serum below quantitative thresholds after a single dose Free Soluble TL1A Free Soluble TL1A Single Dose (SAD) IV and SC Multiple Dose (MAD) IV Placebo Placebo Low dose Low dose Medium dose Medium dose Free sTL1A (pg/mL) Free sTL1A (pg/mL) High dose Weeks Weeks
Slide 26: XmAb942 has favorable immunogenicity profile versus 1st generation anti-TL1A class
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 Duvakitug Tulisokibart
Slide 27: XmAb942 exhibits best-in-class clinical profile versus 1st gen TL1A mAbs
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 12-weeks TL1A Co
Slide 28: XENITH-UC: Global Phase 2b Study of XmAb942
XENITH-UC: Global Phase 2b Study of XmAb942 ® Mark Osterman, M.D., M.S.C.E. SVP & Head of Clinical Development (Autoimmune) Vipul Jairath, MBChB, DPhil, MRCP, FRCPC Professor of Medicine, Division of Gastroenterology Western University, Ontario, Canada Chief Medical Officer, Alimentiv 28
Slide 29: Vipul Jairath, Chief Medical Officer, Alimentiv
Vipul Jairath, MBChB, DPhil, MRCP, FRCPC Chief Medical Officer, Alimentiv Vipul Jairath, MBChB, DPhil, MRCP, FRCPC, oversees the global Medical R&D initiatives and services for alimentiv. In conjunction with the executive team and senior medical advisors, he assumes overall responsibility for alimen
Slide 30: More than 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: Exposure-response across biologic targets is the pharmacological thesis for XENITH-UC
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 at Clinical remi
Slide 32: XmAb942 predicted to maintain higher exposure than other TL1A antibodies
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 integrating cli
Slide 33: XmAb942 predicted to exceed 1st gen benchmarks of TL1A target inhibition
XmAb942 is predicted by quantitative pharmacology model to exceed 1st gen benchmarks of TL1A target inhibition in the XENITH-UC Phase 2b study >99% TL1A Inhibition >90% TL1A Inhibition Molecule Induction (Week 12) Maintenance (Week 52) XmAb942 86% Q12W dosing 90% Afimkibart 40% Q4W 68% Tulisokibart
Slide 34: Favorable XmAb942 clinical convenience in XENITH-UC
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-UC Tulisokibart
Slide 35: 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 36: XmAb412 stands to deliver potential of dual targeting TL1A and IL23p19
XmAb412 stands to deliver the potential of dual targeting TL1A and IL23p19 in a single molecule with convenient subcutaneous dosing DUET-CD study demonstrated benefit of dual XmAb412 robustly suppresses both targeting TNF and IL23p19 in Crohn’s disease1 TL1A and IL23 inflammatory pathways2 αTL1A αIL
Slide 37: TL1A Clinical Strategy & Development Roadmap
TL1A Clinical Strategy & Development Roadmap ® Dane Leone EVP & Chief Strategy Officer 37
Slide 38: Xencor's TL1A clinical strategy is aligned with the 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 39: Xencor's TL1A development roadmap integrates XmAb942 and XmAb412 decision points
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 40: Xencor's IBD portfolio is positioned for value-creating strategic decisions
Xencor’s IBD portfolio is positioned for value-creating strategic decisions Wholly-Owned or Portfolio Acquisition Early Stage Out-License Co-Development PRECEDENT S 1 PRECEDENT S 1 PRECEDENT S 1 $8B+ Market cap2 $900M+ Total Value $10B+ Acquisition $50M Upfront Double-digit royalties $40B+ Market ca
Slide 41: Next clinical development milestones for Xencor's TL1A pipeline
Next clinical development milestones for Xencor’s TL1A pipeline 3Q26 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 XEN
Slide 42: Q&A Session
Q&A Session Bassil Dahiyat, Ph.D. John Desjarlais, Ph.D. President & Chief Executive Officer EVP & Chief Scientific Officer Dane Leone Mark Osterman, M.D., M.S.C.E. SVP & Head of Clinical Development EVP & Chief Strategy Officer (Autoimmune) 42
Slide 43: Results from Phase 1 Study of XmAb942 & TL1A Pipeline Update
Designing Proteins Delivering Medicines ® Results from Phase 1 Study of XmAb942 & TL1A Pipeline Update May 5, 2026