Slide 1: Xencor Q3 2022 Financial Results, XmAb564 Data Presentation
® Xencor Q3 2022 Financial Results XmAb®564 Data Presentation November 7, 2022
Slide 2: Speakers
2 Speakers Bassil Dahiyat, Ph.D. President Chief Executive Officer Director John Kuch Senior Vice President & Chief Financial Officer John Desjarlais, Ph.D. Senior Vice President Chief Scientific Officer Allen Yang, M.D., Ph.D. Senior Vice President Chief Medical Officer Ralph Zitnik, M.D. Executive
Slide 3: Forward-Looking Statements
3 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, stateme
Slide 4: Agenda for Today's Call
4 Agenda for Today’s Call 2 1 3 Recent Business Updates and Financial Results XmAb ® 564 Data Presentation Q&A
Slide 5: XmAb564 Single Dose Phase 1a Data Presentation
® XmAb®564 Single Dose Phase 1a Data Presentation Reduced potency IL2 - Fc For selective expansion of regulatory T cells In development for patients with autoimmune diseases
Slide 6: XmAb Cytokines: Potency-tuned to Enhance Half-life and Tolerability
6 XmAb® Cytokines: Potency - tuned to Enhance Half - life and Tolerability Native cytokine XmAb potency - optimized cytokine - Fc Toxicity Activity Time → Xencor’s general approach for creating cytokine therapies • Overcomes native cytokine short half - life and high toxicity • Systematically engine
Slide 7: XmAb564 Phase 1a Clinical Trial Top-line Data Summary
7 XmAb®564 Phase 1a Clinical Trial Top - line Data Summary • Single ascending dose of subcutaneously administered XmAb564 in healthy volunteers • Well tolerated; no serious adverse events or dose limiting toxicities observed • Selective expansion of CD25 bright regulatory T cells (Tregs) of 10x and
Slide 8: Tregs Important Role in Homeostasis and in Autoimmune Disease
8 Tregs Important Role in Homeostasis and in Autoimmune Disease • Regulatory T cells (Tregs) are CD4 + FoxP3 + cells expressing CD25 (IL - 2R α ) that maintain immune tolerance in tissues by suppressing the function of both CD4 and CD8 effector T cells • Tregs are dysfunctional in most autoimmune di
Slide 9: XmAb564 is Engineered to Improve Selectivity for Treg
9 IL - 2 Activates Multiple T Cell Types XmAb564 is Engineered to Improve for Treg Selectivity Overall 400 - 1000x reduced potency 2x increase to CD25 (IL2R α ) binding and reduced affinity for IL2R β Heterodimeric Fc with Xtend ™ No effector function IL2 Monovalent to avoid undesired activation Tco
Slide 10: XmAb564 Design Reduces Potency and Improves Treg Selectivity
10 10 -1 10 0 10 1 10 2 10 3 10 4 10 5 10 6 10 7 0 1000 2000 3000 Concentration (pM) pSTAT5 MFI CD4+CD45RA+ CD4+CD45RA- Tregs CD8+CD45RA+ CD8+CD45RA- Gamma Delta Cells CD56+ NK cells XmAb564 Design Reduces Potency and Improves Treg Selectivity XmAb564 exhibits extended half - life and good tolerabil
Slide 11: XmAb564 Phase 1a Healthy Volunteer Study Design
11 XmAb564 Phase 1a Healthy Volunteer Study Design Phase 1a single - ascending dose (SAD) study • Randomized and double - blinded • Subcutaneous administration of XmAb564 • Heathy volunteers (n=48) • 6 dose level cohorts • Randomized 6:2 (XmAb564:placebo) Outcome measures • Safety and tolerability •
Slide 12: XmAb564 Was Well Tolerated
12 XmAb564 Was Well Tolerated Well tolerated including at the highest dose evaluated (0.065 mg/kg) • All adverse events (AEs) were grade 1 or 2 (mild - to - moderate) and self - limited • Injection site reaction was the most reported AE • No serious AEs, dose - limiting toxicities or early discontin
Slide 13: XmAb564 Promotes Robust & Durable Expansion of CD25bright Tregs
13 117x 10x 32x 2x ** ** ** ** ** * 21x 6x 6x XmAb564 Promotes Robust & Durable Expansion of CD25 bright Tregs Numeric values in “Peak Fold Change” plot are Mean 1 Peak fold change: Peak CD25 bright FoxP3 + CD4 Treg cell absolute count at a post - treatment time point divided by absolute count at ba
Slide 14: XmAb564 Promotes Robust & Durable Increases in CD25bright Treg/Tcon Ratio
14 0.14 0.04 0.03 0.02 0.01 0.01 0 *** *** *** *** ** * XmAb564 Promotes Robust & Durable Increases in CD25 bright Treg/ Tcon ratio Treg baseline counts are not used in Treg/ Tcon ratio calculations, leading to less variability in ratio values Time Course Peak Ratio Numeric values in “Peak Fold Chan
Slide 15: XmAb564 Promotes Robust & Durable Expansion of Total Tregs
15 8x 2x 4x 3x ** * 5x 2x 3x XmAb564 Promotes Robust & Durable Expansion of Total Tregs Numeric values in “Peak Fold Change” plot are Mean 1 Peak fold change: Peak CD25 + FoxP3 + CD4 Treg cell absolute count at a post - treatment time point divided by absolute count at baseline NS: p>0.05, *: p≤0.05
Slide 16: CD25bright and Total Treg Remain Elevated for at Least 3 Weeks
16 145 26 16 24 33 11 11 *** 65 8 6 ** ** 10 3 3 2 CD25 bright and Total Treg Remain Elevated for at Least 3 Weeks Day 21 CD25 bright Treg Cell Count CD25 hi FoxP3 + CD4 + Numeric values in plots are Mean NS: p>0.05, *: p≤0.05, **: p≤0.01, ***:p≤0.001 compared with placebo treated cohort, Wilcoxon t
Slide 17: XmAb564 Induces Minimal Increases in Conventional T cells and NK Cells
17 XmAb564 Induces Minimal Increases in Conventional T cells and NK Cells CD56 + NK Cell Count CD8 + Tcon Cell Count CD4 + Tcon Cell Count Dashed horizontal blue line represent the average of pre - dose values from all 48 subjects with ± 2SD shown in grey lines
Slide 18: XmAb564 Phase 1a Topline Summary
18 XmAb564 Phase 1a Topline Summary XmAb564 is well tolerated and generates a durable, dose - dependent and selective expansion of Tregs with a single dose • 117 - fold mean peak expansion over baseline in CD25 bright Tregs and 8 - fold mean peak expansion in total Tregs at highest dose • Marked ele
Slide 19: Xencor's Growing Portfolio of Potency-Optimized XmAb Cytokines
19 Xencor’s Growing Portfolio of Potency - Optimized XmAb® Cytokines Second validation of Xencor’s approach to cytokine therapeutics • XmAb306 (IL - 15) Phase 1 demonstrated 40 - to 100 - fold increases in activated NK cells and accumulation upon multiple doses • In two first - in - human studies, r
Slide 20: Q&A
® Q&A
Slide 21: Data Appendix
® Data Appendix
Slide 22: Peak Fold Induction of CD25bright and Total Treg Cells Shows Consistent Dose Response
22 *** 82.3x 16.7x 16.7x *** ** 8.5x 5.7x 5.1x 2.1x *** ** Peak Fold Induction of CD25 bright and Total Treg Cells Shows Consistent Dose Response of Treg Populations to XmAb564 Total Treg Peak Fold Induction 1 CD25 + FoxP3 + CD4 + Numeric value in “Peak Fold Change” plot is Mean 1 Peak fold inductio
Slide 23: Ratio of CD25bright/Tcon and Total Treg/Tcon Peak Fold Induction
23 Ratio of CD25 bright / Tcon and Total Treg/ Tcon Peak Fold Induction Shows Consistent Dose Response of Treg Populations to XmAb564 Numeric value in “Peak Fold Change” plot is Mean Peak fold induction: Peak CD25 bright Treg/ Tcon or total Treg/ Tcon ratios of each subject divided by the average of