Xencor, Inc. · NASDAQ:XNCR
Xencor — Investor Presentation (March 2024)
38 slides from Xencor's investor presentation, Mar 6, 2024
Slide 1: Corporate Overview March 2024
® Proteins by Design® XmAb® Antibody Therapeutics Corporate Overview March 2024
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: Xencor: Engineering Antibody Immune Functions to Make Better Drugs
3 Xencor: Engineering Antibody Immune Functions to Make Better Drugs XmAb® Protein Engineering: small changes, big functional impacts • XmAb Fc Domains augment native immune functions and/or control structure • Preserves half-life, stability and production • Over 1,500 issued patents and pending pat
Slide 4: Layers of Value Creation Built on XmAb Technology
4 Layers of Value Creation Built on XmAb® Technology XmAb® technology platforms have enabled a strong financial foundation and provided technical validation Broad internal clinical-stage pipeline of 3 bispecific antibodies with 1 additional bispecific antibody dosing in 1H 2024 Future waves of pipel
Slide 5: Efficient XmAb Platform Builds Differentiated Pipeline
5 Efficient XmAb® Platform Builds Differentiated Pipeline & Early Clinical Testing Rigorously Vets Lead Programs XmAb technology Early clinical testing Registration-enabling Continually grows drug pipeline Always renewing edge Clinical data drives decisions • Advance internally to late phase and pla
Slide 6: Plug-and-play Fc Domain Enables Rapid Prototyping of Target Combinations
6 Plug-and-play Fc Domain Enables Rapid Prototyping of Target Combinations and Pipeline Generation XmAb® Bispecific Fc Domains Retain Beneficial Antibody Properties XmAb® Cytokines XmAb® Bispecific Antibodies Enable Multiple Classes of New Biologics Highly stable, modular scaffold Antibody-like half
Slide 7: Pipeline Focus on T-Cell Engagers and Vudalimab
7 Pipeline Focus on T-Cell Engagers and Vudalimab XmAb technology enables selective target engagement and increases addressable target space Program (Targets/Design) Fc Domain Indications Preclinical Phase 1 Phase 2 Phase 3 Commercial Rights T Cell Selective, Dual Checkpoint Inhibitor Vudalimab PD-1
Slide 8: XmAb Technologies Create Numerous Differentiated Antibodies for Technology Partners
8 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 Xevudy® Xtend COVID-19 Obexelimab Immune Inhib
Slide 9: XmAb Bispecific Fc Domain
9 ® XmAb® Bispecific Fc Domain Enabling New Classes of Biologics and Therapeutic Mechanisms of Action
Slide 10: Distinct and Novel Mechanisms-of-Action Enabled By XmAb Bispecific Fc Domain
10 Distinct and Novel Mechanisms-of-Action Enabled By Xencor’s XmAb® Bispecific Fc Domain PD-1 CTLA-4 Tumor associated antigen (TAA) vudalimab Efbalropendekin alfa (XmAb306) Targeted Cytokines Tumor Cell Cytotoxic T Cell CD3 and CD28 T Cell Engagers T cell activation (i.e., CD3 or CD28) T Cell Selec
Slide 11: XmAb Bispecific T Cell Engagers
11 ® 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 12: XmAb T Cell Engagers Use Multiple Formats and Affinity Designs
12 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 C
Slide 13: XmAb 2+1 T-cell Engager Clinical Experience: Xaluritamig
13 XmAb® 2+1 T-cell Engager Clinical Experience: Xaluritamig (AMG 509; STEAP1 x CD3) • First TCE to target STEAP1, a challenging membrane target with limited extracellular exposure • Phase 1 expansion & optimization ongoing; Amgen plans to initiate additional studies in earlier treatment lines • Saf
Slide 14: XmAb819: CD3 T-cell Engager for Renal Cell Carcinoma in Phase 1
14 XmAb®819: CD3 T-cell Engager for Renal Cell Carcinoma in Phase 1 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 • Relapsed/refractory clear cell RCC (ccRCC) • Nearly uniformly high E
Slide 15: XmAb541: CD3 T-cell Engager for Ovarian Cancer & Solid Tumors
15 XmAb®541: CD3 T-cell Engager for Ovarian Cancer & Solid Tumors XmAb541 (CLDN6 x CD3) CLDN6 Avoids Normal TissueXmAb 2+1 Design 0.1 1 10 100 1000 10000 100000 0 20 40 60 80 100 0 5 10 15 20 Ab concentration [ng/ml] % Z o m b ie + o n H u tu 8 0 ( C L D N 6 + ) % Z o m b ie + o n 2 9 3 -T R E X (C
Slide 16: CD28 Bispecific Antibodies Provide a Boost to T Cell Activation
16 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 17: XmAb808: Tumor-specific CD28 T-cell Engager Targeted to B7-H3
17 XmAb808: Tumor-specific CD28 T-cell Engager Targeted to Broadly Expressed Tumor Antigen B7-H3 in Phase 1 Clinical Programs XmAb808: Phase 1 dose-escalation in solid tumors • Combination with anti-PD1 (Signal 1); pembrolizumab added on third dose, included in all dose escalation cohorts • Enrollin
Slide 18: T Cell Selective, Dual Checkpoint Inhibitor Vudalimab (PD-1 x CTLA-4)
18 ® T Cell Selective, Dual Checkpoint Inhibitor Vudalimab (PD-1 x CTLA-4)
Slide 19: Vudalimab: Selective PD-1 x CTLA-4 Bispecific Antibody
19 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 20: Evolution of Vudalimab Development Program for mCRPC
20 Evolution of Vudalimab Development Program for mCRPC 2021 2022 2023 2024 Phase 2 Vudalimab + chemotherapy or PARPi in molecularly defined mCRPC Phase 2 Vudalimab monotherapy in high-risk mCRPC cohort Phase 1 Vudalimab dose-escalation and expansion study in mixed solid tumors mCRPC Cohort in Study
Slide 21: Preliminary Data for Vudalimab Monotherapy in mCRPC
21 Preliminary Data for Vudalimab Monotherapy in mCRPC 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 observations of durable responses (41 and 27 weeks) in Phase 1 mCRPC cohor
Slide 22: Phase 1b/2 Study in 1L NSCLC in combination with chemotherapy
22 Phase 1b/2 Study in 1L NSCLC in combination with chemotherapy Part 1 dose comparison, Part 2 randomized vs. pembro; First patient dosed in Q4 2023 Encouraging proof-of-concept data in NSCLC supports evaluation of vudalimab in 1L • Study of volrustomig (PD-1 x CTLA-4) in checkpoint-naïve NSCLC sho
Slide 23: Progress Across XmAb Portfolio Programs in 2024
23 Progress Across XmAb® Portfolio Programs in 2024 Data update and go-forward decision on vudalimab monotherapy (mCRPC) in 1H 2025 XmAb808 B7-H3 x CD28 XmAb819 ENPP3 x CD3 XmAb662 IL12-Fc Complete internal data package from Phase 1 study during 1H 2024 XmAb541 CLDN6 x CD3 Dose first patient during
Slide 24: Corporate Overview March 2024
® Proteins by Design® XmAb® Antibody Therapeutics Corporate Overview March 2024
Slide 25: Vudalimab Monotherapy in Patients with mCRPC
®Vudalimab Monotherapy in Patients with mCRPC Study XmAb717-05 Data cut 7 February 2024
Slide 26: Evolution of Vudalimab Development Program for mCRPC
26 Evolution of Vudalimab Development Program for mCRPC 2021 2022 2023 2024 Phase 2 Vudalimab + chemotherapy or PARPi in molecularly defined mCRPC Phase 2 Vudalimab monotherapy in high-risk mCRPC cohort Phase 1 Vudalimab dose-escalation and expansion study in mixed solid tumors mCRPC Cohort in Study
Slide 27: Summary of Preliminary Data
27 Summary of Preliminary Data 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 observations of durable responses (41 and 27 weeks) in Phase 1 mCRPC cohort in 2 patients with vis
Slide 28: Demographics and Baseline Characteristics and Prior Treatment
28 Demographics and Baseline Characteristics and Prior Treatment Data cut 7 February 2024 Characteristic mCRPC (n = 14) Age, median (range) 72 (58-89) Liver or Lung metastases at baseline, (%) 6 (42.9) PSA (ng/ml) at baseline, median (range) 152.9 (35-1873) ECOG 1, n (%) 12 (85.7) Metastatic disease
Slide 29: Response to Treatment and Percent Change in Target Lesions
29 Response to Treatment and Percent Change in Target Lesions RECIST 1.1 (PCWG3), n (%) mCRPC (n = 12*) Objective response rate 4 (33) Best overall response Complete response 0 Partial response 4 (33) Confirmed 3 (25) Unconfirmed 1 (8) Stable disease 2 (17) Progressive disease 3 (25) Not evaluable 3
Slide 30: Best Percent Change in PSA From Baseline
30 Best Percent Change in PSA From Baseline Data cut 7 February 2024 25% of patients achieved PSA90 PSA90 = PSA reduction ≥ 90% n=12 cPR cPR cPRSD
Slide 31: Characteristics of Patients with Clinical Response
31 Characteristics of Patients with Clinical Response Patient Age/ Race Prior Systemic Therapies Prior Radiation Metastases at Baseline PSA (ng/mL) BOR/ Duration of Response EOT reason 50509 66/AA Docetaxel Enzalutamide Abiraterone None Bone Extrapelvic LN Pelvic LN (SoD = 45.1 mm) Baseline: 165 Nad
Slide 32: Time on Treatment
32 SD 50503 cPR 50502 cPR 50509 uPR 50506 PD* 50510 SD 50504 SD at 4w, PD 50508 cPR 50501 No imaging 50507 SD at 5w 50505 SD at 4w 50511 SD at 5w 50514 PD 50512 No imaging 50513 Time on Treatment (n=14) RECIST 1.1: end of Cycle 2 then Q6W through Cycle 8, Q9W thereafter. Bone scans: end of cycle 2,
Slide 33: Summary of Treatment-Emergent Adverse Events
33 Summary of Treatment-Emergent Adverse Events Event, n (%) mCRPC (n = 14) Any 13 (92.9) Grade ≥ 3 9 (64.3) Treatment related 9 (64.3) Serious adverse event 7 (50.0) Related serious adverse event 4 (28.6) Leading to dose modification* 8 (57.1) Leading to treatment discontinuation 2 (14.3) Leading t
Slide 34: irAEs of Any Grade and Grade 3 or Higher
34 irAEs of Any Grade in ≥ 2 Patients and Grade ≥ 3 in Any Patients Any Grade, n (%) mCRPC (n = 14) Number of subjects with ≥ 1 event 8 (57.1) Rash maculo-papular 4 (28.6) ALT increased 3 (21.4) Amylase increased 2 (14.3) AST increased 2 (14.3) Blood bilirubin increased 2 (14.3) Hyperthyroidism 2 (1
Slide 35: Benchmark Rates of Immune-Mediated Hepatitis
35 Benchmark Rates of Immune-Mediated Hepatitis Drug (Target) Vudalimab (PD-1 x CTLA-4) Ipilimumab (CTLA-4) Ipilimumab (CTLA-4) Ipilimumab (CTLA-4) + Nivolumab (PD-1) Ipilimumab (CTLA-4) + Nivolumab (PD-1) Dosage N=218*, includes 10 mg/kg Q2W & 1000 mg/1200mg Q3W 3 mg/kg 10 mg/kg 1 mg/kg ipilimumab
Slide 36: Novel Therapeutic Development Landscape for mCRPC
36 Novel Therapeutic Development Landscape for mCRPC Drug Vudalimab[1] Xaluritamig[2] Pluvicto + SoC[3] Lorigerlimab[4] MK-5684 (ODM-208)[5] ARX517[6] Vobramitamab Duocarmazine[7] Study Phase 2 FIH / Dose Escalation Phase 3 (VISION) Phase 1 Expansion Cohort Phase 2 Phase 1b Dose Expansion Phase 1 Ex
Slide 37: Novel Therapeutic Development Landscape for mCRPC - Sources
37 Novel Therapeutic Development Landscape for mCRPC - Sources
Slide 38: Vudalimab Monotherapy in Patients with mCRPC
®Vudalimab Monotherapy in Patients with mCRPC Study XmAb717-05 Data cut 7 February 2024