Xencor, Inc. · NASDAQ:XNCR
Xencor — Investor Presentation (January 2025)
35 slides from Xencor's investor presentation, Jan 13, 2025
Slide 1: XmAb Antibody Therapeutics Corporate Overview January 2025
® Proteins by Design® XmAb® Antibody Therapeutics Corporate Overview January 2025
Slide 2: Forward-Looking Statements
2 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 3: Proven Power of XmAb Engineering: Proteins By Design
3 • 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 with over 1,600 patents issued and pending worldwide • Oncology:
Slide 4: Xencor's Disciplined Drug Development Strategy
4 World-leading protein engineers and proven XmAb® Fc platforms, supported by strong financial position of approximately $707 million* Experienced drug development team deliver rapid proof-of-concept clinical studies Rapidly prototype and optimize XmAb® drug candidates, designed with purpose to solv
Slide 5: XmAb Drug Candidate Pipeline
5 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 XmAb808 B7-H3 x CD28 2+1 Bispecific, Xtend Prostate cancer, oncology XmAb541 CLDN6 x CD3 2+1 Bispecific, Xtend Ovari
Slide 6: XmAb Technologies Create Differentiated Antibodies for Technology Partners
6 XmAb® Technologies Create Numerous Differentiated Antibodies for Technology Partners Selected Programs Fc Domain Indications Preclinical Phase 1 Phase 2 Phase 3 Marketed Commercial Rights Ultomiris® Xtend PNH, aHUS, gMG, NMOSD Monjuvi® Cytotoxic DLBCL Obexelimab Immune Inhibitor IgG4-RD, wAIHA Tob
Slide 7: XmAb Bispecific T Cell Engagers
7 ® XmAb® Bispecific T Cell Engagers XmAb 2+1 Bispecific Antibody Format XmAb819 (ENPP3 x CD3) XmAb541 (CLDN6 x CD3) XmAb808 (B7-H3 x CD28)
Slide 8: XmAb T Cell Engagers Use Multiple Formats and Affinity Designs
8 XmAb® T Cell Engagers Use Multiple Formats and Affinity Designs to Customize for Each Tumor Target 1 ScFv Targets: CD3 or CD28 Targets: tumor antigen (e.g., ENPP3, STEAP1, Claudin 18.2, B7-H3)Targets: tumor antigen (e.g., CD20, CD38) Examples Xaluritamig CD3 ASP2138 CD3 XmAb819 CD3 XmAb541 CD3 CD3
Slide 9: XmAb819: CD3 T-cell Engager for Renal Cell Carcinoma in Phase 1
9 XmAb®819: CD3 T-cell Engager for Renal Cell Carcinoma in Phase 1 Encouraging Initial Data in Ongoing Dose Escalation in ccRCC XmAb819 (ENPP3 x CD3) Phase 1 Dose Escalation Study Selective T cell directed cytotoxicity Hi ENPP3 Lo ENPP3 XmAb 2+1 Design ENPP3: high RCC; low healthy tissues • Dose esc
Slide 10: XmAb541: CD3 T-cell Engager for Ovarian Cancer & Solid Tumors
10 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 11: XmAb541 Engineered for High Selectivity Against CLDN6
11 XmAb541 Extensively Engineered for High Selectivity Against CLDN6 Versus Closest Family Members 0.1 1 10 10 0 10 00 10 00 0 10 00 00 10 00 00 0 0 5000 10000 Conc. (ng/mL) M FI (A F6 47 ) CLDN17 CLDN8 CLDN4 CLDN3 CLDN9 CLDN6 0.5 1.5 2.0 0.5 1.5 2.0 Normalized CLND6 Binding N or m al iz ed C LD N 9
Slide 12: CD28 Bispecific Antibodies Provide a Boost to T Cell Activation
12 CD28 Bispecific Antibodies Provide a Boost to T Cell Activation XmAb® CD28 T cell engagers feature low affinity, monovalent binding • Avoid historic CD28 safety concerns (superagonism) • Well behaved: stable, silent FcγR interactions, with Xtend Fc technology • Potential to combine with anti-PD1
Slide 13: XmAb808: Tumor-specific CD28 T-cell Engager Targeting B7-H3
13 XmAb808: Tumor-specific CD28 T-cell Engager Targeted to Broadly Expressed Tumor Antigen B7-H3 in Phase 1 Phase 1 Dose Escalation Study • Dose-escalation cohorts are continuing per protocol1, enrolling patients with multiple tumor types (prostate, ovarian, HNSCC, urothelial and others), majority w
Slide 14: New Pipeline Programs: B-cell Depleting T-cell Engagers
14 ® New Pipeline Programs: B-cell Depleting T-cell Engagers Plamotamab (CD20 x CD3) XmAb657 (CD19 x CD3)
Slide 15: Well Validated Targets and Bispecific Formats Could Enable New Biology
15 Well Validated Targets and Bispecific Antibody Formats Could Enable New Biology to Create Breakthrough Medicines Combination therapy using two approved antibodies showed additive efficacy in Phase 2 in colitis (Janssen) and new real-world multicenter studies Highly potent B-cell depletion demonst
Slide 16: Deep B-Cell Depletion with T-cell Engagers Could Reset the Immune System
16 Deep B-Cell Depletion with T-cell Engagers Could Help “Reset” the Immune System for Patients with Autoimmune Disease B-cell antigen (e.g., CD19, CD20) B-cell depletion T-cell activation against autoreactive B cell XmAb® Bispecific Antibody Autoreactive B-Cell Diseases1 Cytotoxic perforins & granz
Slide 17: CD20 & CD19 TCEs Can Address Unmet Needs for Autoimmune Disease
17 XmAb® CD20 & CD19 TCEs Can Address Significant Unmet Needs for Autoimmune Disease Responsive to Targeted B-Cell Depletion1 Currently >$20bn in annual disease modifying drug spend for treatment of rheumatoid arthritis within the US12 Ocrevus the market leader in US/EU5 with 24% global patient shar
Slide 18: Plamotamab: Phase Ready Subcutaneous CD20 x CD3 BsAb
18 Plamotamab Phase 2 Ready, Subcutaneous CD20 x CD3 BsAb Positioned for SuccessXmAb® CD20 x CD3 Bispecific Design • Plamotamab designed in a 1+1 format and selected for extended activity and favorable tolerability observed in NHPs • Human half-life ~18 days; estimated 80% SC bioavailability • Robus
Slide 19: Plamotamab in NHPs: Durable B-cell Depletion
19 Day 0 (Predose) Day 4 Day 8 Day 30 0 1 2 3 B ce ll / T c el l ( C D 40 + / C D 8+ ) Low dose High dose Single Dose of Plamotamab in NHPs Durable B-cell Depletion Observed in Blood and Lymphoid Organs Blood B cells Lymph node B cellsBone marrow B cells Days post-dose C D 40 + B c el ls (v s ba se
Slide 20: >95-99% Peripheral B-cell Depletion in Lymphoma Patients with Plamotamab
20 >95-99% Peripheral B-cell Depletion Observed in Lymphoma Patients with IV & SC Plamotamab in 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 % R ed uc tio n in B -c el l C ou nt b y Fl ow C yt
Slide 21: Plamotamab: Plan for Phase 1b/2a RA Study Start
21 Plamotamab: Plan for Phase 1b/2a RA Study Start Maximal efficiency to clinical proof of concept in rheumatoid arthritis • Quickly refine priming/step-up dosing regimens used in lymphoma studies • Assess SC and IV routes, and pre-medication regimen including corticosteroids, to be run in parallel
Slide 22: XmAb657: CD19 x CD3 Optimized for Autoimmune Disease
22 Positioned for SuccessRational XmAb® Design XmAb657: CD19 x CD3 Optimized for Autoimmune Disease Bispecific Fc Domain Ongoing NHP studies have shown effective B-cell depletion with single dose • Broad opportunity set of disease indications supports multiple development pathways for success • EULA
Slide 23: XmAb657 in NHPs: Deep B-cell Depletion Sustained for 28 Days
23 0 7 14 21 28 0 20 40 60 80 100 5000 10000 Days post administration B c el ls /μ L of b lo od Single Dose of XmAb657 in NHPs Deep B-cell Depletion Sustained for at Least 28 Days XmAb 657 Single IV Dose (low) XmAb657 Single IV Dose (high) * * * * * * * *** Peripheral blood 0 7 14 21 28 0 20 40 60 8
Slide 24: XmAb657: Rationally Designed for Autoimmune Disease, FIH Planned 2H'25
24 XmAb657: Rationally Designed for Autoimmune Disease FIH Planned 2H’25 • Has been observed to demonstrate deep and durable B-cell depletion in NHPs, enabled by potentially best-in-class pharmacokinetics • Has been well tolerated in NHP with no clinical signs of CRS • GMP production campaign initia
Slide 25: New Pipeline Programs: TL1A Portfolio
25 ® New Pipeline Programs: TL1A Portfolio XmAb942 (Xtend TL1A) XmAb TL1A x IL-23
Slide 26: Inflammatory Bowel Disease is a Devastating Disease with Unmet Need
26 Inflammatory Bowel Disease (IBD) is a Devastating Disease with Significant Unmet Medical Need Abdominal pain Diarrhea Rectal bleeding Weight loss 1 Clarivate 2 GlobalData 3 Prescient whitepaper Global IBD drug spend projected to be $23bn+ by 20302 Two common forms: Crohn’s disease Ulcerative
Slide 27: Development of XmAb942 and XmAb TL1A x IL-23 for IBD
27 Development of XmAb942 and XmAb TL1A x IL-23 for IBD Phase 2 TL1A Studies and VEGA Study Support Strategy XmAb942 Design XmAb TL1A x IL-23 Design Xtend + FcKO Bispecific Fc Domain • Building upon proof-of-concept studies with TL1A targeted therapy and combination therapies for the treatment of Ul
Slide 28: Xtend Fc: Validated Half-Life Extension Technology
28 Xtend Fc: Validated Half-Life Extension (HLE) Technology Enabling Potential Best-in-Class Anti-TL1A Clinically validated with significantly improved half-life and dose frequency • Ultomiris half-life extended >4x as compared to Soliris; maintenance dose frequency reduced by 4X1 • VRC01LS half-lif
Slide 29: XmAb942: Novel High-Affinity Anti-TL1A mAb with Extended Half-Life
29 XmAb942: Novel High-Affinity Anti-TL1A mAb Designed for Extended Half-Life, Under Development for the Treatment of IBD • XmAb942 utilizes Xtend Fc domain technology with potentially class-leading potency • Half-life in non-human primate studies, 23 days, supports Q8W to Q12W dosing in humans • Hi
Slide 30: XmAb TL1A x IL-23 to Have First-in-Class Potential
30 XmAb® TL1A x IL-23 to Have First-in-Class Potential First-in-Human Study Planned in 2026 TL1A Activity 0.0 01 0.0 1 0.1 1 10 10 0 1 2 3 4 Concentration (nM) Fo ld in du ct io n IL-23 Activity • Rapidly prototype in multiple formats • Optimize and tune for biological activity • Lead selection in 2
Slide 31: T Cell Selective, Dual Checkpoint Inhibitor Vudalimab (PD-1 x CTLA-4)
31 ® T Cell Selective, Dual Checkpoint Inhibitor Vudalimab (PD-1 x CTLA-4)
Slide 32: Vudalimab: Selective PD-1 x CTLA-4 Bispecific Antibody
32 Vudalimab: Selective PD-1 x CTLA-4 Bispecific Antibody • Monotherapy generally well tolerated, with a potentially differentiated profile from two-antibody combination therapy (PD-1 + CTLA-4) • Xencor’s initial focus on tumors with poor PD-1 inhibitor activity: e.g., prostate cancer anti-PD-1 scFv
Slide 33: Vudalimab Development Program for mCRPC and NSCLC
33 Vudalimab Development Program for mCRPC and NSCLC XmAb717-05: Phase 2 vudalimab monotherapy in high-risk mCRPC cohort Vudalimab monotherapy has been associated with clinical response in 5 out of 12 evaluable mCRPC patients with visceral or lymph node metastases • Findings consistent with observat
Slide 34: Potential Inflection Points for Xencor's Clinical Portfolio in 2025
34 Potential Inflection Points for Xencor’s Clinical Portfolio in 2025 XmAb Drug Candidate Indication Oncology Portfolio Vudalimab PD-1 x CTLA-4 mCRPC NSCLC XmAb819 ENPP3 x CD3 ccRCC Initiation of dose expansion XmAb808 B7-H3 x CD28 Solid tumor Initiation of dose expansion Ovarian+XmAb541 CLDN6 x CD
Slide 35: XmAb Antibody Therapeutics Corporate Overview January 2025
® Proteins by Design® XmAb® Antibody Therapeutics Corporate Overview January 2025