Xencor XmAb819 yields partial responses in 5 of 11
A potential registration-enabling study of XmAb819 is planned by the end of 2027.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Filing Summary
Xencor, Inc. reported updated Phase 1 results for XmAb819, an ENPP3 x CD3 bispecific antibody studied in advanced clear cell renal cell carcinoma (ccRCC). At the October 1, 2026 data cut, the 400 mcg/kg cohort had 5 confirmed partial responses among 11 efficacy-evaluable patients (45.5% cORR), a 55% unconfirmed response rate (uORR), and an 82% six-month Kaplan-Meier PFS estimate. Xencor selected 400 mcg/kg as the proposed intravenous recommended Phase 3 dose.
Across 68 expansion-dose patients, 72.1% had Grade 3 or higher related treatment-emergent adverse events; 5.9% discontinued because of related events. Common Grade 3 or higher events included AST increased (35.3%), ALT increased (33.8%), and rash (22.1%).
Xencor plans to discuss a potential accelerated-approval pathway with FDA in the first half of 2027 and a global randomized trial comparing XmAb819 with tivozanib. Xencor says the study, if successful and subject to further FDA interactions, could support full approval. Based on current operating plans, Xencor expects cash to fund research and development programs and operations into 2029.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Positive
- Minor pointThe 400 mcg/kg cohort reported a 45.5% cORR among 11 patients.
Negative
- Moderate pointGrade 3 or higher related TEAEs affected 72.1% of 68 expansion-dose patients.
Filing Explained
The expansion-dose safety analysis covers 68 patients and excludes one who received about 10 times the intended exposure, developed Grade 4 CRS, recovered and stopped treatment; Xencor also reports suspected dose-preparation errors in 3 of 69 patients.
8-K Event Classification
Key Figures
Key Terms
confirmed objective response rate (cORR) medical
recommended Phase 3 dose (RP3D) medical
cytokine release syndrome (CRS) medical
Kaplan-Meier estimate medical
accelerated approval pathway regulatory
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What XmAb819 response results did XNCR report at 400 mcg/kg?
What adverse events were reported in XNCR's XmAb819 expansion cohorts?
What are XNCR's next development plans for XmAb819?
AI-generated analysis. How Rhea-AI works. Not financial advice.
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02. Results of Operations and Financial Condition.
Based on current operating plans, Xencor, Inc. (the “Company”) expects to have cash to fund research and development programs and operations into 2029.
Forward-Looking Statements
The statement in this Item 2.02 of this Current Report on Form 8-K regarding the period through which the Company expects its cash to fund its research and development programs and operations is a forward-looking statement within the meaning of the Private Securities Litigation Reform Act of 1995. This statement is based on the Company’s current operating plans and assumptions and is subject to risks and uncertainties that could cause actual results to differ materially, including changes in the Company’s operating plans, the timing, cost and results of clinical trials, unanticipated expenses, the receipt and timing of collaboration and licensing revenue, and the other risks described under “Risk Factors” in the Company’s most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. The Company may use its available capital resources sooner than it currently expects. This statement speaks only as of the date of this Current Report on Form 8-K, and the Company undertakes no obligation to update it, except as required by law.
The information furnished under this Item 2.02 of this Current Report on Form 8-K shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or incorporated by reference in any filing under the Securities Act of 1933, as amended (the “Securities Act”), or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
Item 7.01. Regulation FD Disclosure.
On October 26, 2026, the Company posted a presentation on the “Investors” section of the Company’s website (www.xencor.com), which includes a description of the updated results from the Phase 1 study of XmAb819, an ENPP3 x CD3 T-cell engaging bispecific antibody, in patients with advanced clear cell renal cell carcinoma. The information contained in, or that can be accessed through, the Company’s website is not a part of this filing. A copy of the presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K and incorporated herein by reference. The presentation is current as of October 26, 2026, and the Company disclaims any obligation to update, supplement or amend this material.
The information furnished under this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1 hereto, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or incorporated by reference in any filing under the Securities Act or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
Item 8.01. Other Events.
On October 25, 2026, the Company issued a press release announcing updated results from the Phase 1 study of XmAb819, an ENPP3 x CD3 T-cell engaging bispecific antibody, in patients with advanced clear cell renal cell carcinoma. A copy of the press release is filed as Exhibit 99.2 to this Current Report on Form 8-K and incorporated herein by reference.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. | Description | |
| 99.1 | Presentation dated October 26, 2026. | |
| 99.2 | Press release issued by Xencor, Inc. on October 25, 2026. | |
| 104 | Cover Page Interactive Data File, formatted in Inline Extensible Business Reporting Language (iXBRL). |
1
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: October 26, 2026 | XENCOR, INC. | |
| By: | /s/ Celia Eckert | |
| Celia Eckert | ||
| General Counsel & Corporate Secretary | ||
2
Exhibit 99.1
® Designing Proteins Delivering Medicines Updated Results from Dose Expansion Cohorts in the Phase 1 Study of XmAb819 October 26, 2026
2 Today's Speakers Bassil Dahiyat, Ph.D. President & Chief Executive Officer Xencor Management Guest Speaker Sumanta Pal, M.D., F.A.S.C.O. Professor, Department of Medical Oncology & Therapeutics Research Vice Chair of Academic Affairs Co-director, Kidney Cancer Program City of Hope Comprehensive Cancer Center Dane Leone Executive Vice President & Chief Strategy Officer John Desjarlais, Ph.D. Executive Vice President & Chief Scientific Officer Jeff Chou Senior Vice President, Head of Oncology Clinical Development
3 Today's Agenda XmAb819 development strategy Updated Phase 1 results of XmAb819, a novel ENPP3 x CD3 bispecific, in advanced clear cell renal cell carcinoma (ccRCC) Overview & XmAb® 2+1 T-cell Engagers Summary and Q&A Additional results
4 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 regarding Xencor's development plans and timelines; potential regulatory actions; expected use of cash resources; the timing and results of clinical trials; the plans and objectives of management for future operations; and the potential markets for Xencor's product and development candidates. Forward-looking statements are based on the current expectations of management and upon what management believes to be reasonable assumptions based on information currently available to it, and involve numerous risks and uncertainties, many of which are beyond Xencor's control. These risks and uncertainties could cause future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Such risks include, but are not limited to, potential delays in development timelines or negative preclinical or clinical trial results, reliance on third parties for development efforts and changes in the competitive landscape including changes in the standard of care for treatment of diseases for which we are developing product candidates, as well as other risks described in Xencor's filings with the Securities and Exchange Commission, including Xencor's most recent Annual Report on Form 10-K and subsequently filed Quarterly Reports on Form 10-Q. Xencor expressly disclaims any duty, obligation or undertaking to update or revise any forward-looking statements contained herein to reflect any change in Xencor's expectations with regard thereto or any subsequent change in events, conditions or circumstances on which any such statements are based, except in accordance with applicable securities laws. For all forward-looking statements, we claim the protection of the safe harbor for forward looking statements contained in the Private Securities Litigation Reform Act of 1995. Disclaimer: We use our trademarks and our logo in this presentation. This presentation also includes trademarks, tradenames and service marks that are the property of other organizations. Solely for convenience, trademarks and tradenames referred to in this presentation appear without the "®" and "TM" symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or that the applicable owner will not assert its rights, to these trademarks and tradenames.
5 Xencor is at the forefront of bispecific T-cell engagers in solid tumors with the 3rd late-stage XmAb® program expected in 2027 XmAb819 ENPP3 x CD3 Planned, potential registration-enabling study start in 2027 Advanced ccRCC and ENPP3+ tumors 100% Wholly Owned Xaluritamig STEAP1 x CD3 Phase 3 Prostate cancer, Ewing sarcoma Mid- to high-single digit royalty and up to $225 million in milestone payments1 ASP2138 CLDN18.2 x CD3 Phase 3 Gastric/GEJ cancer, Pancreatic cancer High single- to low double-digit royalty and up to $232.5 million in milestone payments1 XmAb® Fc Domains Augment native immune functions in molecules and/or control their structure, while preserving desired attributes (e.g., Xtend extended half-life or heterodimeric Fc domain for bispecific antibodies). XmAb® toolkits enable rapid prototyping and lead optimization XmAb® 2+1 Formats Designed to enable antibodies to bind more avidly and selectively kill cells with higher antigen density, potentially sparing normal cells XmAb® 2+1 programs in solid tumor oncology advancing internally and with leading pharmaceutical partners 1 Remaining as of June 30, 2026 ccRCC clear cell renal cell carcinoma GEJ gastro-esophageal junction
6 Oncology Clinical Studies Our focus on clinical excellence to realize value from XmAb® platform Cash runway into 2029 2024 2026 2025 2027 (Planned) Solid Tumor Oncology ccRCC clear cell renal cell carcinoma Exp expansion FIH first-in-human HGSOC high-grade serous ovarian carcinoma IBD inflammatory bowel disease IIM idiopathic inflammatory myopathies SjD Sjögren's disease SSc systemic sclerosis RA rheumatoid arthritis Autoimmune Clinical Studies Autoimmune Programs XmAb819 ccRCC & ENPP3+ Tumors Dose and Indication Expansions Dose Escalation Initiate Phase 3 study of XmAb819 in ccRCC XmAb541 + XmAb808 HGSOC Preclinical '541 Monotherapy Dose Escalation '541 FIH Study '541 + '808 Dose escalation of combination FIH Study Phase 2b XENITH-UC Preclinical Primary endpoint analysis in ~2H27 XmAb942 IBD FIH Study Preclinical Initial Phase 1 data in 1H27 Initiate Phase 2 studies XmAb412 IBD Phase 1b Dose Escalation in RA Ongoing dose escalation Data update Xencor regains rights to develop plamotamab Plamotamab Rheumatoid Arthritis FIH Study Preclinical Ongoing dose escalation Data update Xencor regains rights to develop new CD19- targeted antibodies XmAb657 IIM, SjD, SSc Ph 1 Final data Ph 1 Exp data Ph 1 Initial data Preclinical Final data Ph 1 Initial data
7 ® XmAb® 2+1 T Cell Engagers
8 Solid tumor targeting challenge: target expression on normal tissues XmAb® 2+1 format aims to combine tumor selectivity with high potency to treat aggressive cancers Low potency / High selectivity High potency / High selectivity Low potency / Low selectivity High potency / Low selectivity Low High Anti-tumor Potency Tumor Selectivity Low High ADC antibody drug conjugate BiTE® is a registered trademark of Amgen Inc. TCE T-cell engager 1st gen TCE (e.g. BiTE®) Monoclonal Antibodies Chemotherapy ADCs Next-gen TCE (XmAb® 2+1)
9 Tuned XmAb® 2+1 formats potentially improve selectivity of T-cell engagers in solid tumors Tumor cell Normal cell 1+1 format 1+1 high affinity needed to bind tumor cells Also binds normal cells 1+1 format XmAb 2+1 high avidity/low affinity target binding Selective for tumor cells Tumor cell Normal cell High density tumor cell Low density normal cell XmAb 2+1 format XmAb 2+1 format > ~
10 Tuned XmAb® 2+1 formats potentially improve selectivity of T-cell engagers in solid tumors Tumor cell Normal cell 1+1 format 1+1 high affinity needed to bind tumor cells Also binds normal cells 1+1 kills both tumor and normal cells tumor normal XmAb 2+1 high avidity/low affinity target binding Selective for tumor cells Tumor cell High density tumor cell Low density normal cell XmAb 2+1 format Normal cell 2+1 kills tumor cells, spares normal cells QSP cytotoxicity models tumor normal QSP quantitative systems pharmacology
11 XmAb819 is an XmAb® 2+1 ENPP3 x CD3 bispecific antibody in development for ccRCC αCD3 αENPP3 αENPP3 1 10 100 1000 10000 0 20 40 60 80 mAb [ng/mL] % Cytotoxicity Preferential killing of ENPP3high cells in vitro High ENPP3 Low ENPP3 Full length 2+1 antibody-like format 0 5 10 15 20 0 250 500 750 1000 1250 Days post dose 1 tumor volume anti-PD1 PBS XmAb819 (300 μg/kg) Strong in vivo activity in PD1-refractory model ccRCC clear cell renal cell carcinoma Affinity/avidity tuned High tumor/normal selectivity
12 XmAb819 targets ENPP3 for treatment of renal cell carcinoma and other solid tumors ENPP3 is strongly expressed in ccRCC and in subsets of other histologies ccRCC pRCC CRC NSCLC (Ad) ccRCC clear cell renal cell carcinoma CRC colorectal cancer IDC invasive ductal carcinoma NSCLC non-small cell lung cancer pRCC papillary renal cell carcinoma RCC renal cell carcinoma 0 200 400 H- Score n=8 50 100
13 XmAb® engineering: modular, stable and tuned for purpose Highly stable – Long half-life – Standard manufacturing Engineer robust, soluble, variable and Fc domain modules Fv domains Fc domains Tune affinity and other properties for specific use Affinity series Epitope series Assemble modules into required format
14 XmAb819 PK profile supports Q2W+ dosing schedule • Well characterized by a two compartment PopPK model • Linear clearance and dose proportional exposure • ~1000x range of doses • Terminal half life ~ 8 days • Quantitative Systems Pharmacology (QSP) Model • 100 µg/kg and 200 µg/kg doses maintained drug concentration above EC50 • 400 µg/kg maintained drug concentration above EC80 * QSP modeled cytotoxicity range * PK pharmacokinetic(s) popPK population PK Q2W every two weeks
15 XmAb819 late-phase manufacturing activities initiated Modular XmAb design and expert CMC execution create scalable process and stable product Robust process Highly stable Supply chain Cell bank – well characterized, high titer Drug substance (DS) – Xencor platform process 2000L scale Drug product (DP) – Multiple presentations for flex across IV/SC dose range DS – 60 months (anticipate 60+) DP – 60 months (anticipate 60+) Liquid formulation 5 ⁰C U.S. manufacturing at validated commercial CDMOs CDMO contract development and manufacturing organization CMC chemistry, manufacturing and control(s) IV intravenous SC subcutaneous
Phase 1 results of XmAb819, a novel ENPP3 x CD3 bispecific, in advanced clear cell renal cell carcinoma (ccRCC) Sumanta K. Pal1, Benjamin Garmezy2, Randy F. Sweis3, Mehmet A. Bilen4, Scott S. Tykodi5, Yuanquan Yang6, Karie Runcie7, David A. Braun8, David J. VanderWeele9, Claud M. Grigg10, Christopher Hoimes11, Adanma Ayanambakkam12, Joseph J. Maly13, Robert A. Franklin14, Biren Saraiya15, Chet Bohac16, Jitendra Kanodia16, Nicholas Rinella16, Ritesh R. Kotecha17, Laurence Albiges18 25 October 2026 Abstract 2684 1City of Hope Comprehensive Cancer Center, Duarte, USA; 2Sarah Cannon Research Institute, Nashville, USA, 3University of Chicago, Chicago, USA, 4Winship Cancer Institute of Emory University, Atlanta, USA, 5University of Washington and Fred Hutchinson Cancer Center, Seattle, USA, 6The Ohio State University Comprehensive Cancer Center, Columbus, USA, 7Columbia University, New York, USA, 8Yale School of Medicine, New Haven, USA, 9Northwestern University, Chicago, USA, 10Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Charlotte, NC, USA, 11Duke University Medical Center, Durham, USA, 12University of Oklahoma Health Sciences Center, Oklahoma City, USA, 13Norton Cancer Institute - St Matthews Campus, Louisville, USA, 14University of Cincinnati Medical Center, Cincinnati, OH, USA, 15Rutgers Cancer Institute, New Brunswick, USA, 16Xencor, Inc., Pasadena, California, USA, 17 Memorial Sloan Kettering Cancer Center, New York, USA, 18Institut Gustave Roussy, Villejuif, France Reused with permission from the European Society for Medical Oncology. © 2026 The Authors. All rights reserved. Officially licensed by ESMO for distribution via Xencor.
Pal SK, et al. XmAb819, ENPP3 x CD3 bispecific antibody in development for ccRCC ENPP3 ectonucleotide pyrophosphatase / phosphodiesterase family member 3 1Doñate, Fernando, et al. Clinical Cancer Research 22.8 (2016) • ENPP3 is an extracellular nucleotide metabolizing enzyme with high expression in RCC and other solid tumors, and low expression in normal tissues1 • XmAb 2+1 format selectively binds and kills high density ENPP3 tumor cells, but spares low density normal tissue • XmAb819 targets T cells for potent lysis of ENPP3+ tumor cells
XmAb819-01: Phase 1 study design in advanced ccRCC Key Eligibility Criteria • R/R ccRCC – prior ICI & VEGFR-TKI • Measurable disease by RECIST v1.1 • No prior anti-ENPP3 therapy Endpoints • Primary: Safety & Tolerability • Secondary: • ORR, DOR, PFS per RECIST 1.1 • Pharmacokinetics NCT05433142. US & EU sites. Eight dose levels explored below expansion (n = 51) Study Schema – IV Administration Screening Priming Step-Up Step-Up TD Day 99 TD TD TD TD TD TD TD 85 71 57 43 36 29 22 15 8 1 Cycle 1 Cycle 2 Cycle 3 DOR, duration of response; ICI, immune checkpoint inhibitor; IV, intravenous; ORR, objective response rate; PFS, progression free survival; R/R, relapsed / refractory; TD, target dose; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor 100 μg/kg Complete n = 11 n = 30 n = 27 Dose Escalation Dose Expansion 200 μg/kg Complete Enrolling 400 μg/kg Outcomes reported in current presentation. Pal SK, et al.
Patient characteristics Baseline Characteristic All IV Doses (n=119) Expansion Doses (n=68) Median Age, Years (range) 61 (34, 78) 62 (34, 78) Male, n (%) 97 (81.5) 58 (85.3) Race – White, n (%) 101 (84.9) 56 (82.4) Time Since Disease Diagnosis, mo. (range) 52.5 (7, 287) 49.5 (7, 287) IMDC Risk Score at Baseline1, n (%) Favorable 8 (6.7) 4 (5.9) Intermediate 81 (68.1) 46 (67.6) Poor 30 (25.2) 18 (26.5) Sarcomatoid Features, n (%) 16 (13.4) 13 (19.1) ≥3 Metastatic Sites, n (%) 84 (70.6) 46 (67.6) Bone metastasis, n (%) 58 (48.7) 32 (47.1) Liver metastasis, n (%) 48 (40.3) 27 (39.7) Target Lesions SOD (mm), Median 90.0 90.5 ENPP3 Positive From Cases With Tissues2 (%) 83/89 (93.3) 50/52 (96.2) Prior Therapy All IV Doses (n=119) Expansion Doses (n=68) # Prior Regimens, Median (Min, Max) 3 (1, 10) 3 (1, 10) 1, n (%) 7 (5.9) 4 (5.9) 2 35 (29.4) 22 (32.4) 3 30 (25.2) 18 (26.5) ≥4 47 (39.5) 24 (35.3) Prior Treatments, n (%) Any Immune Checkpoint Inhibitor 119 (100) 68 (100) Any VEGFR-TKI 119 (100) 68 (100) 2 or More VEGFR-TKIs 76 (63.9) 43 (63.2) HIF2α Inhibitor 42 (35.3) 23 (33.8) Nephrectomy, n (%) 81 (68.1) 46 (67.6) HIF2α, hypoxia-inducible factor 2-alpha; IMDC, International Metastatic RCC Database Consortium; IHC, immunohistochemistry; SOD, sum of diameters; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor Subjects who received ≥1 protocol-specified dose of XmAb819 were included in the baseline characteristics analysis. Data cut-off: 01 September 2026. Excludes 1 participant who experienced approximately 10-fold higher exposure than intended at the first and only dose administered, and who subsequently developed Grade 4 CRS and discontinued treatment. 1IMDC risk derived at study baseline using central laboratory values; KPS <80% defined as ECOG ≥2. 2Tumor ENPP3 positivity was defined as a tumor proportion score (TPS) ≥1, regardless of expression intensity, by a clinical trial IHC assay (Roche Diagnostics). Pal SK, et al.
Adverse events Expansion Doses (n=68) Any Incidence >Day 29 Onset Preferred Term, n (%) All grades Grade ≥3 All grades Grade ≥3 Rash (combined term)1 62 (91.2) 15 (22.1) 20 (29.4) 2 (2.9) Cytokine release syndrome 46 (67.6) 4 (5.9) 12 (17.6) 1 (1.5) ALT increased 36 (52.9) 23 (33.8) 12 (17.6) 7 (10.3) Nausea 35 (51.5) - 9 (13.2) - AST increased 33 (48.5) 24 (35.3) 10 (14.7) 6 (8.8) Oedema peripheral 31 (45.6) - 11 (16.2) - Vomiting 30 (44.1) - 7 (10.3) - Diarrhoea 28 (41.2) 2 (2.9) 9 (13.2) 2 (2.9) Fatigue 27 (39.7) - 11 (16.2) - Headache 23 (33.8) - 10 (14.7) - Hypophosphataemia 20 (29.4) 1 (1.5) 8 (11.8) - Hypotension 20 (29.4) 5 (7.4) 3 (4.4) 1 (1.5) Pruritus 19 (27.9) - 7 (10.3) - Chills 18 (26.5) - 11 (16.2) - Cough 18 (26.5) - 10 (14.7) - TEAEs reported in >25% Subjects by Maximum Severity Grade ALT, alanine aminotransferase; ASTCT, American Society for Transplantation and Cellular Therapy; AST, aspartate aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event; TEAE, treatment-emergent adverse event Number of Subjects With, n (%) All IV Doses (N=119) Expansion Doses (n=68) Grade ≥ 3 95 (79.8) 56 (82.4) Related TEAE Grade ≥ 3 75 (63.0) 49 (72.1) Serious TEAE 74 (62.2) 42 (61.8) Related Serious TEAE 64 (53.8) 37 (54.4) TEAE Leading to Dose Reduction 7 (5.9) 1 (1.5) Did Not Reach Target Dose 9 (7.6) 3 (4.4) TEAE Leading to Discontinuation 8 (6.7) 5 (7.4) Related TEAE Leading to Discontinuation 7 (5.9) 4 (5.9) Leading to Death 0 0 Summary of Adverse Events 1Combined rash term includes 10 preferred terms: rash (unspecified, maculo-papular, erythematous, macular, morbilliform, pustular, pruritic, anal), erythema, dermatitis acneiform. Subjects who received ≥1 protocol-specified dose of XmAb819 were included in the safety analysis. Data cut-off: 01 September 2026. Excludes 1 participant who experienced approximately 10-fold higher exposure than intended at the first and only dose administered, and who subsequently developed Grade 4 CRS and discontinued treatment. Reported TEAEs were defined per MedDRA and CTCAE; CRS graded per ASTCT2. 2Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638. • Low rate of dose reductions and treatment discontinuation due to TEAEs • Events were predominately confined to the priming dose period • Most common Grade ≥3 TEAEs were asymptomatic, transient transaminase increases Pal SK, et al.
Adverse events Expansion Doses (n=68) Any Incidence >Day 29 Onset Preferred Term, n (%) All grades Grade ≥3 All grades Grade ≥3 Rash (combined term)1 62 (91.2) 15 (22.1) 20 (29.4) 2 (2.9) Cytokine release syndrome 46 (67.6) 4 (5.9) 12 (17.6) 1 (1.5) ALT increased 36 (52.9) 23 (33.8) 12 (17.6) 7 (10.3) Nausea 35 (51.5) - 9 (13.2) - AST increased 33 (48.5) 24 (35.3) 10 (14.7) 6 (8.8) Oedema peripheral 31 (45.6) - 11 (16.2) - Vomiting 30 (44.1) - 7 (10.3) - Diarrhoea 28 (41.2) 2 (2.9) 9 (13.2) 2 (2.9) Fatigue 27 (39.7) - 11 (16.2) - Headache 23 (33.8) - 10 (14.7) - Hypophosphataemia 20 (29.4) 1 (1.5) 8 (11.8) - Hypotension 20 (29.4) 5 (7.4) 3 (4.4) 1 (1.5) Pruritus 19 (27.9) - 7 (10.3) - Chills 18 (26.5) - 11 (16.2) - Cough 18 (26.5) - 10 (14.7) - TEAEs reported in >25% Subjects by Maximum Severity Grade ALT, alanine aminotransferase; ASTCT, American Society for Transplantation and Cellular Therapy; AST, aspartate aminotransferase; CTCAE, Common Terminology Criteria for Adverse Events; MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event; TEAE, treatment-emergent adverse event Number of Subjects With, n (%) All IV Doses (N=119) Expansion Doses (n=68) Grade ≥ 3 95 (79.8) 56 (82.4) Related TEAE Grade ≥ 3 75 (63.0) 49 (72.1) Serious TEAE 74 (62.2) 42 (61.8) Related Serious TEAE 64 (53.8) 37 (54.4) TEAE Leading to Dose Reduction 7 (5.9) 1 (1.5) Did Not Reach Target Dose 9 (7.6) 3 (4.4) TEAE Leading to Discontinuation 8 (6.7) 5 (7.4) Related TEAE Leading to Discontinuation 7 (5.9) 4 (5.9) Leading to Death 0 0 Summary of Adverse Events 1Combined rash term includes 10 preferred terms: rash (unspecified, maculo-papular, erythematous, macular, morbilliform, pustular, pruritic, anal), erythema, dermatitis acneiform. Subjects who received ≥1 protocol-specified dose of XmAb819 were included in the safety analysis. Data cut-off: 01 September 2026. Excludes 1 participant who experienced approximately 10-fold higher exposure than intended at the first and only dose administered, and who subsequently developed Grade 4 CRS and discontinued treatment. Reported TEAEs were defined per MedDRA and CTCAE; CRS graded per ASTCT2. 2Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638. • Low rate of dose reductions and treatment discontinuation due to TEAEs • Events were predominately confined to the priming dose period • Most common Grade ≥3 TEAEs were asymptomatic, transient transaminase increases Pal SK, et al.
Cytokine release syndrome (CRS) • CRS was predominately low-grade and occurred during priming • No dose delays and one treatment discontinuation due to CRS • Premedications for XmAb819: ▪ Acetaminophen, diphenhydramine, and IV normal saline ▪ Dexamethasone prior to priming doses ▪ Tocilizumab prior to priming dose 1 (PD1) • Graded per ASTCT consensus criteria; managed per institutional standards, or NCCN guidelines when local standards were absent Subjects who received ≥1 protocol-specified dose of XmAb819 were included in the safety analysis. Data cut-off: 01 September 2026. Excludes 1 participant who experienced approximately 10-fold higher exposure than intended at the first and only dose administered, and who subsequently developed Grade 4 CRS and discontinued treatment. Reported TEAEs were defined per MedDRA and CTCAE; CRS graded ASTCT1. Per-protocol PK samples were not collected for subject in plot (left) with reported Grade 4 CRS at priming dose 3; drug exposure could not be determined. Two subjects each experienced 2 events of Grade ≥3 CRS. 1Lee DW, et al. Biol Blood Marrow Transplant. 2019;25:625-638. ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome, CTCAE, Common Terminology Criteria for Adverse Events; MedDRA, Medical Dictionary for Regulatory Activities; NCCN, National Comprehensive Cancer Network; PD, priming dose, TEAE, treatment-emergent adverse event; TD, target dose CRS by Max Grade & Dose (n=68) % of Subjects with CRS Dosed, n Pal SK, et al.
Cytokine-driven adverse events Median of the per-subject maximum of ALT and AST (central laboratory), expressed as ×ULN, among subjects with an available result at each timepoint. Data cut-off: 01 September 2026. Rash by Max Grade & Dose (n=68) Transaminase kinetics by Dose (n=68) Combined rash terms (10 PTs): rash (unspecified, maculo-papular, erythematous, macular, morbilliform, pustular, pruritic, anal), erythema, dermatitis acneiform. Reported TEAEs were defined per MedDRA and CTCAE. Data cut-off: 01 September 2026. • Transaminase elevations were asymptomatic, transient, and self-limited, with a median time to resolution of 7 days and no clinical sequelae. • Dose delays due to transaminase elevations occurred in 14.7% of subjects, with no treatment discontinuations. • Rash, an on-target effect due to ENPP3 expression on basophils and mast cells, is well managed with daily antihistamine (oral) and steroids (topical & oral). • Dose delays due to rash occurred in 4.4% of subjects, with no treatment discontinuations. % of Subjects with Rash PD, priming dose; TD, target dose Median x ULN (Max of ALT/AST) Dosed, n Dosed, n Pal SK, et al.
Antitumor activity at target dose of 100 μg/kg Efficacy Evaluable 100 μg/kg (n = 30) Confirmed ORR, % (95% CI) 30.0 (14.7, 49.4) BOR, n (%) CR 1 (3.3) PR 8 (26.7) SD 17 (56.7) PD 4 (13.3) DCR, % (95% CI) 86.7 (69.3, 96.2) Median follow-up, months (range) 4.1 (1.1, 28.3) Efficacy analysis includes subjects with ≥1 protocol-specified dose of XmAb819 and ≥1 post-baseline tumor assessment. Confirmed responses per investigator assessment, RECIST v1.1. Data cut-off: 01 September 2026. CR subject has two resolved lymph node target lesions with residual mass <10 mm. BOR, best overall response; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease; Tx, treatment Study Months Baseline 5 10 15 20 25 30 Best % Change from Baseline % Change from Baseline Ongoing Tx -100 -80 -60 -40 -20 0 20 40 -100 -80 -60 -40 -20 0 20 40 Ongoing Tx Pal SK, et al.
Efficacy analysis includes subjects with ≥1 protocol-specified dose of XmAb819 and ≥1 post-baseline tumor assessment. Confirmed responses per investigator assessment, RECIST v1.1. Data cut-off: 01 September 2026. 1Two subjects at 200 μg/kg discontinued treatment without a post-baseline response assessment and without documented progression. BOR, best overall response; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease; Tx, treatment Efficacy Evaluable1 200 μg/kg (n = 25) Confirmed ORR, % (95% CI) 44.0 (24.4, 65.1) BOR, n (%) CR - PR 11 (44.0) SD 5 (20.0) PD 9 (36.0) DCR, % (95% CI) 64.0 (42.5, 82.0) Median follow-up, months (range) 4.5 (0.8, 11.6) Best % Change from Baseline % Change from Baseline Study Months Baseline 2 4 6 8 10 12 -100 -80 -60 -40 -20 0 20 40 -100 -80 -60 -40 -20 0 20 40 Antitumor activity at target dose of 200 μg/kg Ongoing Tx Ongoing Tx Pal SK, et al.
Efficacy Evaluable 400 μg/kg (n = 11) Confirmed ORR, % (95% CI) 45.5 (16.8, 76.6) BOR, n (%) CR - PR 5 (45.5) SD 4 (36.4) PD 2 (18.2) DCR, % (95% CI) 81.8 (48.2, 97.7) Median follow-up, months (range) 6.0 (1.4, 7.9) Efficacy analysis includes subjects with ≥1 protocol-specified dose of XmAb819 and ≥1 post-baseline tumor assessment. Confirmed responses per investigator assessment, RECIST v1.1. Data cut-off: 01 September 2026. BOR, best overall response; CR, complete response; DCR, disease control rate; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease; Tx, treatment Antitumor activity at target dose of 400 μg/kg Best % Change from Baseline % Change from Baseline Baseline -100 -80 -60 -40 -20 0 20 40 -100 -80 -60 -40 -20 0 20 40 1 2 3 4 5 6 7 8 9 Study Months Ongoing Tx Ongoing Tx Pal SK, et al.
Antitumor activity of 100-400 μg/kg doses in prior therapy subgroups Best % Change from Baseline -100 -80 -60 -40 -20 0 20 40 Best % Change from Baseline -100 -80 -60 -40 -20 0 20 40 Prior HIF2α Inhibitor (n=23) Prior ≥2 VEGFR-TKIs (n=42) Expanded Doses Prior HIF2α (n = 23) ≥2 VEGFR-TKIs (n=42) Confirmed ORR, % (95% CI) 34.8 (16.4, 57.3) 45.2 (29.9, 61.3) DCR, % (95% CI) 78.3 (56.3, 92.5) 85.7 (71.5, 94.6) DCR, disease control rate; HIF2α, hypoxia-inducible factor 2-alpha; ORR, objective response rate; TKI, tyrosine kinase inhibitor; Tx, treatment; VEGFR, vascular endothelial growth factor receptor Efficacy analysis includes subjects with ≥1 protocol-specified dose of XmAb819 and ≥1 post-baseline tumor assessment. Confirmed responses per investigator assessment, RECIST v1.1. Data cut-off: 01 September 2026. CR subject has two resolved lymph node target lesions with residual mass <10 mm. Ongoing Tx Ongoing Tx Pal SK, et al.
Depth and duration of responses Responders Expansion Doses (n=25) Ongoing Responses, n (%) 19 (76.0) Median TTR, months (range) 2.7 (1.3, 20.9) Median time on treatment, months (range) 7.0 (3.4, 28.3) Spider Plot of Confirmed Responders Across All IV Doses (n = 27) % Change from Baseline Study Months TTR, time to response; Tx, treatment Efficacy analysis includes subjects with ≥1 protocol-specified dose of XmAb819 and ≥1 post-baseline tumor assessment. Confirmed responses per investigator assessment, RECIST v1.1. Data cut-off: 01 September 2026. Tx Pal SK, et al.
Pal SK, et al. Patient case study: Deepening of response over time • Background: Male, 57 years old, RCC diagnosed 10 years ago, metastatic disease ~5 years ago • Prior therapy: 2 prior therapy lines cabozantinib + nivolumab (1 mo) → progression & lenvatinib + everolimus (3 yrs) → progression • Baseline: Two enlarged mediastinal lymph nodes both > 2 cm longest diameter multiple small lung and pancreas lesions membrane ENPP3+ <25% tumor cells • Response: PR week 6, deepened to CR week 42 normalization of lymph nodes disappearance of lung and pancreas lesions • Treatment and response ongoing at month 16 Baseline 15.5 Months
Conclusions • XmAb819 (ENPP3 x CD3) showed meaningful antitumor activity in patients with advanced ccRCC. • Antitumor activity was observed in a dose-dependent manner, with a cORR of 30% at 100 μg/kg, 44% at 200 μg/kg, and 45% at 400 μg/kg, and a majority of responses ongoing at data cut. • Consistent activity in subgroups with prior exposure to HIF2α inhibitors (cORR 35%) and ≥2 VEGFR-TKIs (cORR 45%). • These data support continued development of XmAb819 as a monotherapy for advanced clear cell RCC and evaluation of rational combination strategies in earlier lines of treatment. cORR, confirmed objective response rate; HIF2α, hypoxia-inducible factor 2-alpha; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor receptor Pal SK, et al.
31 ® Additional Results
32 Durable disease control observed in heavily pre-treated advanced ccRCC population 7.9 month median time-on-treatment1 Current follow-up for the consolidated IV target dose patient population (expanded doses: 100, 200 and 400 µg/kg) n=66; 95% CI: 5.8, 13.4 Data-cut: 01-Oct-2026 1 Kaplan-Meier estimate of time-on-treatment defined as censor as of last treatment date or first event of progressive disease or death ccRCC clear cell renal cell carcinoma CI confidence interval Number of months
33 Tx Deepening of response and new responses over time were common • Consistent with sustained T-cell activation and low adverse event rate after priming period • Combination of rapid disease control with potential for longer term deepening of response • Response profile matured over several cycles: 25% of responders >4.2 months TTR Time to Response (TTR) % of Responders >1.4 mo 75 >2.7 mo 50 >4.2 mo 25 Spider Plot of Confirmed Responders Across All IV Doses (n = 27) % Change from Baseline Study Months TTR analysis for n=25 patients in Expanded Doses. Data cut-off: 01 September 2026.
34 • 45% cORR plus additional week 42 conversion of a stable disease patient to uPR (uORR 55%) • >80% DCR, low rate of primary progressive disease • >70% of patients with treatment ongoing • ~82% 6-month PFS K-M estimate at follow-up • Median PFS is Not Reached • Safety results: 400 μg/kg consistent with 200 μg/kg and 100 μg/kg target dose cohorts • Enrollment complete in 400 μg/kg expansion cohort • Data from the full 400 µg/kg IV analysis set expected during 1H2027 (20+ patients) Data-cut: 01-Oct-2026 cORR confirmed objective response rate DCR disease control rate IV intravenous K-M Kaplan-Meier PFS progression free survival RP3D recommended Phase 3 dose uORR unconfirmed objective response rate uPR unconfirmed partial response 400 μg/kg target dose is the proposed IV RP3D for XmAb819
35 Global randomized control trial with a tivozanib control arm could potentially support BLA submission seeking a post IO-TKI label1 3L sub-group analysis of TiNivo-2 provides a basis for expectations of standard dose tivozanib outcomes in a contemporary post IO-TKI patient population 1 Study design and registrational potential subject to further interactions with FDA 2 Final analysis of the TiNivo-2 phase 3 trial: Long-term outcome of Tivozanib (Tivo) in patients with metastatic renal cell carcinoma (mRCC); Motzer and Choueiri et al; ASCO 2026. BICR blinded independent central review BLA biologics license application DOR duration of response HR hazard ratio IO immuno-oncology K-M Kaplan-Meier ORR objective response rate OS overall survival PFS progression free survival QD every day RECIST response evaluation criteria in solid tumors TKI tyrosine kinase inhibitor VEGFR VEGF receptor Arm B Arm A Screening Period Randomization powered for ~0.70 HR on PFS XmAb819 Tivozanib PFS Interim Analysis PFS Primary Analysis and Overall Survival Follow-Up Patient Population • Prior exposure to one PD-1 or PD-L1 inhibitor and one VEGFR-TKI End Points • Primary: PFS per RECIST 1.1 by BICR, OS • Secondary: ORR & DOR per RECIST 1.1 by BICR, safety & tolerability Tivozanib reported (TiNivo-2)2 • Median PFS of 5.44 months (2.1 – 7.36) • 6-month PFS K-M estimate of ~41% • ORR of 10.5% (4.3, 20.4) Proposed Phase 3 study design to evaluate XmAb819 compared to tivozanib in post IO-TKI patient population
36 ® XmAb819 Development Strategy
37 45% XmAb819 400 µg/kg Target Dose 33% 32% 31% 31% Cabozantinib CABOSUN Pazopanib VEG105192 Pazopanib COMPARZ Sunitinib Motzer 2007 23% 19% 17% Nivolumab CheckMate 025 Axitinib AXIS Cabozantinib METEOR 22% 18% Belzutifan LITESPARK-005 Tivozanib TIVO-3 4L 1L 2L 3L+ 1 Cross-trial comparison for illustration only and is not based on head-to-head studies; trials differ in design, population and response assessment, and strong caution should be exercised when comparing data across unrelated trials. Comparators: AXIS Rini Lancet 2011 CABOSUN Choueiri JCO 2017; investigator-assessed, 20% by IRC CheckMate 025 Motzer Cancer 2020 COMPARZ Motzer NEJM 2013; Motzer NEJM 2007 LITESPARK-005 Choueiri NEJM 2024; 1–3 prior regimens METEOR Choueiri Lancet Oncol 2016 TIVO-3 Rini Lancet Oncol 2020 VEG105192 Sternberg JCO 2010, treatment-naïve subgroup ccRCC clear cell renal cell carcinoma XmAb819 XmAb819-01 Phase 1, 400 µg/kg IV target dose (Data cut Oct 01, 2026) cORR confirmed objective response rate NCCN National Comprehensive Cancer Network ORR objective response rate 45% cORR in advanced ccRCC exceeds monotherapy benchmarks despite a more heavily pre-treated patient population ORR for XmAb819 compared to NCCN guideline recommended monotherapy treatments for advanced ccRCC1 17–23% ORR for approved 2L/3L+ options
38 XmAb819 Phase 1 study, 400 µg/kg IV 82% +27% Cabozantinib METEOR 57% +3% Axitinib AXIS 70% -3% Tivozanib TIVO-3 80% -4% Belzutifan LITESPARK-005 78% -12% Nivolumab CheckMate 025 65% -12% 18% 14% 22% 22% 34% 35% 45% 17% 19% 18% 22% 23% XmAb819 high objective response rate relative to primary progression supports earlier line development as a monotherapy treatment 1 Cross-trial comparison for illustration only and is not based on head-to-head studies; trials differ in design, population and response assessment, and strong caution should be exercised when comparing data across unrelated trials 2 Risk group per IMDC or MSKCC as reported by each trial Comparators: AXIS Rini Lancet 2011 CheckMate 025 Motzer NEJM 2015 LITESPARK-005 Choueiri NEJM 2024 METEOR Choueiri NEJM 2015 TIVO-3 Rini Lancet Oncol 2020 XmAb819 XmAb819-01 Phase 1, all treated patients (Data-cut 01-Oct-2026) XmAb819 demonstrated favorable balance of response to primary progressive disease despite enrolling a poorer prognosis patient population Agent / trial1 Intermediate- to-poor risk2 ◄ Primary progression Objective response ► Net (ORR − PD)
39 7% 6% 9% 10% 16% 21% Belzutifan (LITESPARK-005) XmAb819 (Phase 1) Axitinib (AXIS) Cabozantinib (METEOR) Nivolumab (CheckMate 025) Tivozanib (TIVO-3) 1 Cross-trial comparison for illustration only and is not based on head-to-head studies; trials differ in design, population, exposure duration and AE attribution (any-cause vs. treatment-related), and strong caution should be exercised when comparing data across unrelated trials. Comparators: AXIS Rini Lancet 2011 CheckMate 025 Motzer NEJM 2015 LITESPARK-005 Choueiri NEJM 2024 METEOR Choueiri NEJM 2015 TIVO-3 Rini Lancet Oncol 2020 XmAb819 XmAb819-01 Phase 1, all treated patients (Data-cut 01-Oct-2026) ccRCC clear cell renal cell carcinoma Treatment-emergent adverse events (TEAEs) leading to discontinuation, % of patients1 XmAb819 was well tolerated with a low rate of discontinuations due to adverse events compared to third party studies of approved monotherapy ccRCC therapies Fewer discontinuations compared with those reported in certain studies of most approved later-line therapies, with no dose reductions required for toxicity management at target dose
40 Xencor plans to discuss accelerated approval pathway for XmAb819 based on efficacy results in key sub-groups Best % Change from Baseline -100 -80 -60 -40 -20 0 20 40 Prior IO, ≥2 VEGFR-TKIs +/- Prior HIF2α Inhibitor (n=42) DCR, disease control rate; HIF2α, hypoxia-inducible factor 2-alpha; ORR, objective response rate; TKI, tyrosine kinase inhibitor; Tx, treatment; VEGFR, vascular endothelial growth factor receptor Efficacy analysis includes subjects with ≥1 protocol-specified dose of XmAb819 and ≥1 post-baseline tumor assessment. Confirmed responses per investigator assessment, RECIST v1.1. Data cut-off: 01 September 2026. CR subject has two resolved lymph node target lesions with residual mass <10 mm. Ongoing Tx • No guideline-recommended treatments exist post PD-1/PD-L1 inhibitor plus ≥2 VEGFR-TKIs, or post PD-1/PD-L1 inhibitor, VEGFR-TKI, and HIF2α inhibitor (triple-class exposed) • Estimated addressable population of ~9,200 US patients who were treated post PD-1/PD-L1 inhibitor and ≥2 prior VEGFR- TKIs in 20251 • Triple-class exposed population is smaller but growing, driven by approval of belzutifan + lenvatinib post PD-1/PD-L1 inhibitor (LITESPARK-011) Expanded Doses Prior HIF2α (n = 23) ≥2 VEGFR-TKIs (n=42) Confirmed ORR, % (95% CI) 34.8 (16.4, 57.3) 45.2 (29.9, 61.3) DCR, % (95% CI) 78.3 (56.3, 92.5) 85.7 (71.5, 94.6) 1 Komodo Health claims data; nationally weighted U.S. patient estimates for 2025
41 Q3W IV / reduced hospitalization Planned Increase Clinical Convenience 1 Komodo Health claims data; nationally weighted U.S. patient estimates for 2025 ccRCC clear cell renal cell carcinoma IO immuno-oncology IV intravenous TCE T-cell engager TKI tyrosine kinase inhibitor SC subcutaneous Q3W every 3 weeks 1H first-half SC monotherapy Post-IO + TKI Status Ongoing Expected Milestone or Readout End of Phase 1 meeting 1H 2027 Development plan for XmAb819 to become the backbone of ccRCC treatment Patient population A & B A & E Description Post Front-line IO-IO for IMDC Intermediate – Poor Risk Patients 2L ccRCC Post-1L nivolumab/ipilimumab (TKI-naïve) ~9.4K Ongoing Proof of concept data 2027 Status Expected Milestone or Readout U.S. Patient opportunity1 Patient population D Description Phase 1 Part Nivolumab combination 1L opportunity for novel IO-TCE combination ~30.1K Planned PD-1 Proof-of-concept Combination for Future 1L study Status U.S. Patient opportunity1 Patient population F Description Phase 1 Part Phase 1 Part Post-IO + TKI – Establish XmAb819 Monotherapy Post IO-TKI IV monotherapy Post-IO + TKI ~23.9K Ongoing End of Phase 1 meeting 1H 2027 A & B Status Expected Milestone or Readout U.S. Patient opportunity1 Description Patient population Phase 1 Part
42 ~$5B 1 cabozantinib, lenvatinib, axitinib, sunitinib, pazopanib, tivozanib ~$5.6B 2 nivolumab, pembrolizumab, ipilimumab, avelumab ~$1.1B 3 belzutifan TKI 43% IO 48% HIF2α 9% 1 Estimate based on 2025 cabozantinib net product revenue and RCC market share internal estimates from Xencor 2 Estimate based on annualized Q2'26 global nivolumab sales and Komodo RCC market claims data 3 Estimate based on annualized Q2'26 global belzutifan sales IO immuno-oncology RCC renal cell carcinoma TKI tyrosine kinase inhibitor Global RCC drug market is an estimated ~$11.7B annualized opportunity TKI Class IO Class HIF2α Class
43 U.S. 2030 TAM in ENPP3+¹ papillary RCC, MSS colorectal cancer and NSCLC +$4.5B 1 Estimates for U.S. ENPP3+ population based on H-Score of ≥25 cutoff CRC colorectal cancer FTD/TPI trifluridine/tipiracil IO immuno-oncology MSS microsatellite stable NSCLC non-small cell lung cancer SoC standard of care TAM total addressable market 2L/3L Papillary RCC U.S. 2030 TAM ~$0.5B > 50% ENPP3+1 SoC: cabozantinib 3L MSS Colorectal Cancer U.S. 2030 TAM +$1B > 50% ENPP3+1 SoC: regorafenib, fruquintinib or FTD/TPI + bevacizumab 2L/3L NSCLC U.S. 2030 TAM +$3B > 30% ENPP3+1 SoC: docetaxel post IO and/or targeted therapy for actionable mutations ENPP3+ expansion programs add significant development opportunities Enrolling patients with pRCC, MSS CRC and NSCLC in Part C of the ongoing Phase 1 study
44 Expected 2027 plans include first potential registration - enabling study in ccRCC and further data from ongoing Phase 1 study cohorts Initiation of first registration - enabling study targeted by YE2027 YE 2027 2027 Present first data from post 1L IO - IO for IMDC intermediate/poor risk patients Continue enrollment of ENPP3+ basket study (pRCC, CRC and NSCLC) End of Phase 1 meeting to inform potential accelerated approval pathway and design for potential global RCT using tivozanib control arm to support BLA seeking potential full approval following a PD(L)1 inhibitor and VEGFR - TKI 1H 2027 Present subcutaneous dosing and full 400 μg/kg intravenous dosing cohort data 1H 2027 ccRCC clear cell renal cell carcinoma CRC colorectal cancer IMDC International mRCC Database Consortium IO immuno - oncology NSCLC non small cell lung cancer pRCC papillary renal cell carcinoma RCT randomized control trial TKI tyrosine kinase inhibitor VEGFR VEGF receptor YE year - end 1H first - half
45 Focus on clinical excellence is expected to deliver an accelerating pace of readouts across Xencor's pipeline through 2027 XmAb® Drug Candidate Indication Oncology Portfolio 2H2026 2027 (Planned) Autoimmune Portfolio As of 26-Oct-2026 ACR American College of Rheumatology (Convergence 2026) ccRCC clear cell renal cell carcinoma CRC colorectal cancer FIH first-in-human HGSOC high-grade serous ovarian carcinoma IBD inflammatory bowel disease IIM idiopathic inflammatory myopathies NSCLC non-small cell lung cancer pRCC papillary renal cell carcinoma RA rheumatoid arthritis RP3D recommended Phase 3 dose XmAb819 ENPP3 x CD3 Additional ENPP3+ tumors Initiate tumor expansion cohorts for CRC, NSCLC and pRCC Present RP3D monotherapy data at ESMO 2026 CLDN6+ HGSOC XmAb541 CLDN6 x CD3 + XmAb808 + B7-H3 x CD28 Safety and early assessment of efficacy XmAb942 Xtend TL1A IBD+ Update on progress achieved in Phase 2b XENITH-UC study ~YE26 XmAb412 TL1A x IL23p19 IBD+ Initiate first-in-human study Plamotamab CD20 x CD3 Rheumatoid arthritis Initial dose-escalation data from ongoing Phase 1b in RA at ACR XmAb657 CD19 x CD3 IIM, Sjögren's disease, Systemic sclerosis Update on progress achieved in FIH dose-escalation study ccRCC Ongoing dose escalation Initiate registration-enabling study Safety and early assessment of efficacy Primary endpoint analysis in ~2H27 Phase 1 data Initiate Phase 2 Studies Updated data from ongoing escalation Updated data from ongoing escalation
46 ® Q&A
® Designing Proteins Delivering Medicines Updated Results from Dose Expansion Cohorts in the Phase 1 Study of XmAb819 October 26, 2026
Exhibit 99.2
Xencor Presents Phase 1 Dose Selection Data for XmAb819, a Potential First-in-Class ENPP3 x CD3 Bispecific T-Cell Engager, in Development for Patients With Advanced Clear Cell Renal Cell Carcinoma and ENPP3+ Tumors
-- 400 mcg/kg chosen as proposed IV RP3D based on 45.5% cORR, 55% uORR and 82% 6-month PFS Kaplan-Meier estimate --
-- Xencor plans to discuss a potential accelerated approval pathway with the FDA in key ccRCC patient subgroups in 1H2027 --
-- Xencor plans global randomized study of monotherapy XmAb819 compared to tivozanib in a post PD-(L)1 and VEGFR TKI ccRCC patient population --
-- Management to host webcast Monday, October 26 at 7:00 a.m. ET / 4:00 a.m. PT --
PASADENA, Calif.--Oct. 25, 2026-- Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and autoimmune diseases, today announced updated results from the Phase 1 study of XmAb819, an ENPP3 x CD3 T-cell engaging bispecific antibody, in patients with advanced clear cell renal cell carcinoma (ccRCC). The results were presented by Sumanta Pal, M.D., FASCO, professor and vice chair of academic affairs at City of Hope Comprehensive Cancer Center, in a proffered paper oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, Spain. Xencor also reported additional follow-up data supporting selection of 400 mcg/kg as the intravenous proposed recommended Phase 3 dose and outlined plans for potential registration-enabling development by the end of 2027.
“We are excited to share the XmAb819 Phase 1 dose expansion results presented at ESMO today, along with key additional data, supporting the potential to bring T-cell engagement to treatment of patients with advanced clear cell renal cell carcinoma. We plan to initiate a potential registration-enabling study next year,” said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. “XmAb819 exemplifies our approach to engineering XmAb 2+1 bispecific antibodies for selective targeting of malignant cells in solid tumors, and we anticipate that it will become the third XmAb 2+1 candidate to advance into late-stage development. With cash runway into 2029, we are well positioned to continue to pursue an accelerated pace of clinical development across our portfolios in oncology and autoimmune disease.”
“XmAb819 has demonstrated impressive antitumor activity in a heavily pre-treated and difficult-to-treat patient population with advanced clear cell renal cell carcinoma,” said Dr. Pal, who is also a study investigator. “At present, available treatments for renal cell carcinoma include checkpoint inhibitors and targeted therapies along the VEGF axis. XmAb819 is an agent with a wholly distinct proposed mechanism of action as a potential first-in-class ENPP3-targeted T-cell engager. Given the unique proposed mechanism as well as the efficacy and tolerability results we have seen thus far, it is critical to explore this agent in earlier settings and in other ENPP3-expressing malignancies.”
Xencor will host a webcast tomorrow at 7:00 a.m. ET (4:00 a.m. PT) to discuss the updated results presented at ESMO, additional data and development plans for XmAb819. The live webcast may be accessed through this link and through “Events & Presentations” in the Investors section of the Company’s website, located at investors.xencor.com. A recording will be available for at least 30 days.
Updated Phase 1 Results of XmAb819 Presented at ESMO
As of the September 1, 2026 data-cut, the Phase 1 study enrolled a total of 119 patients with advanced ccRCC across 11 different intravenous (IV) target dose levels. XmAb819 is administered as a weekly priming regimen with escalating priming doses followed by the maintenance target dose.
Three target dose levels were chosen for expansion and evaluation as a proposed recommended Phase 3 dose (RP3D), 100 mcg/kg, 200 mcg/kg and 400 mcg/kg (Expansion Doses, n=68). Patients enrolled into the Expansion Dose cohorts were heavily pre-treated with a median of three prior lines of therapy and were predominantly intermediate- to poor-risk (94%) by the IMDC (International Metastatic RCC Database Consortium) risk model. All patients had received at least one prior PD-(L)1 inhibitor and at least one prior VEGFR TKI. In addition, 63% of patients were previously treated with two or more prior VEGFR TKIs, and 34% of patients were treated with at least one HIF2α inhibitor. Response rate increased with increasing dose across Expansion Doses, and all Expansion Doses were generally well tolerated.
| Expansion Dose Cohort, n1 | 100 mcg/kg n=30 | 200 mcg/kg n=25 | 400 mcg/kg n=11 | |||||||||
| Confirmed Objective Response Rate (cORR)2 (95% CI) | 30% (14.7% – 49.4%) | 44% (24.4% – 65.1%) | 45.5% (16.8% – 76.6%) | |||||||||
| Disease Control Rate (95% CI) | 87% (69.3% – 96.2%) | 64% (42.5% – 82%) | 82% (48.2% – 97.7%) | |||||||||
| Median Follow-up (months) | 4.1 | 4.5 | 6 |
| 1. | Efficacy analysis includes patients with at least one protocol-specified dose of XmAb819 and at least one post-baseline tumor assessment. Two patients enrolled into the 200 mcg/kg cohort are excluded due to not having a post-baseline tumor assessment, and one patient enrolled into the 400 mcg/kg cohort is excluded for never receiving a protocol-specified dose of XmAb819. |
| 2. | Confirmed responses per investigator assessment, RECIST v1.1. |
Of the 25 patients with confirmed response per RECIST v1.1, one had a complete response, 24 had partial responses and 19 of the responses remained ongoing as of the data cut with a median time on treatment of 7 months (range, 3.4 – 28.3).
XmAb819 was generally well tolerated in the combined Expansion Dose cohorts with manageable adverse events and a low 5.9% rate of treatment discontinuation due to related treatment-emergent adverse events (TEAEs). Grade 3 or higher related TEAEs occurred in 72.1% of patients. The most common Grade 3 or higher TEAEs were liver enzyme elevations (aspartate aminotransferase (AST) increased, 35.3%; alanine aminotransferase (ALT) increased, 33.8%), rash (combined term, 22.1%), hypotension (7.4%) and cytokine release syndrome (CRS, 5.9%). TEAEs occurred primarily during the priming period, and after day 29 the most common Grade 3 or higher TEAEs that occurred were liver enzyme elevations (ALT increased, 10.3%; AST increased, 8.8%), rash (combined term, 2.9%) and diarrhea (2.9%).
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Cytokine-related adverse events, such as CRS, rash and liver enzyme elevations, were well managed, transient and had limited impact on treatment. CRS did not lead to dose delays, and one patient discontinued treatment due to CRS. Rash (combined term) led to dose delays in 4.4% of patients with no treatment discontinuations. Transaminase elevations were asymptomatic, transient, and self-limited, with a median time to resolution of seven days and no clinical sequelae; dose delays occurred in 14.7% of patients with no treatment discontinuations.
Suspected dose preparation errors were limited to three patients in the Expansion Dose cohorts (3/69 patients). The Expansion Dose analysis set excludes one patient who never received a protocol-specified dose of XmAb819, experienced an approximately 10-fold higher exposure than intended at the first and only dose administered, subsequently developed Grade 4 CRS, fully recovered and discontinued treatment. All three events occurred prior to introduction of the new study drug formulation.
Management to Discuss Additional Data and Development Plans on Webcast
As of a subsequent October 1, 2026 data-cut, the current efficacy evaluable cohort (n=11) at 400 mcg/kg IV reported 5 confirmed partial responses (cORR, 45.5%) and 1 unconfirmed partial response (uORR, 55%). The median progression-free survival (PFS) estimate was not reached, and more than 70% of patients remained on treatment. The 6-month Kaplan-Meier estimate of PFS was 82%. The safety results were consistent with the 100 mcg/kg and 200 mcg/kg target dose cohorts.
Xencor has selected the IV dose of 400 mcg/kg as the proposed IV RP3D for advanced clinical development. The decision is based on maturing data from the efficacy evaluable cohort (n=11) and with additional patients who have enrolled into this expansion cohort. Xencor anticipates a total efficacy-evaluable patient population treated at 400 mcg/kg of at least 20 patients to be available to support dose selection during the first half of 2027.
Xencor plans to discuss a potential accelerated approval pathway with the FDA in subsets of patients with advanced ccRCC who have exhausted standard of care. A pooled analysis of the three Expansion Doses provided two patient subsets, patients who had progressed after prior treatment exposure to at least one PD-(L)1 inhibitor and at least two VEGFR TKIs (n=42) and “triple class exposed” patients with prior treatment exposure to at least one PD-(L)1 inhibitor, one VEGFR TKI and one HIF2α inhibitor (n=23).
As of the September 1, 2026 data-cut:
| ● | Efficacy evaluable patients enrolled with prior treatment exposure to at least one PD-(L)1 inhibitor and at least 2 or more VEGFR TKIs reported 18 confirmed partial responses and 1 confirmed complete response (45% cORR; 95% CI, 29.9% – 61.3%). |
| ● | Efficacy evaluable “triple class exposed” patients with prior treatment exposure to at least one PD-(L)1 inhibitor, one VEGFR TKI and one HIF2α inhibitor reported 8 confirmed partial responses (35% cORR; 95% CI, 16.4% – 57.3%). |
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Xencor plans to initiate a global randomized trial comparing XmAb819 with tivozanib as a control arm in advanced ccRCC patients who have prior treatment with one PD-(L)1 inhibitor and at least one VEGFR TKI. Xencor anticipates that, subject to further interactions with FDA, this study, if successful, could serve as the basis for full approval of XmAb819 as a monotherapy in the second- and third-line treatment setting for patients with advanced ccRCC. In a sub-group analysis of the TiNivo-2 study in a similar treatment line (patients who were post PD-(L)1 and at least one VEGFR TKI), tivozanib achieved a median PFS of 5.4 months, a 6-month PFS Kaplan-Meier estimate of 41% and a cORR of 10.5%.1
Proof-of-concept sub-studies to enable expansion of XmAb819 development are ongoing.
| ● | Dose escalation of subcutaneous administration in advanced ccRCC is ongoing, with anticipated results during the first half of 2027. |
| ● | Part C of the ongoing Phase 1 study is enrolling patients with ENPP3+ advanced papillary RCC, colorectal cancer and non-small cell lung cancer. |
| ● | Part D of the ongoing Phase 1 study is enrolling patients with IMDC intermediate- to poor-risk ccRCC, who have progressed after nivolumab in combination with ipilimumab as a first-line treatment and are naïve to VEGFR TKI therapy. |
| ● | Part F of the ongoing Phase 1 study is planned as a safety study for the combination of XmAb819 with nivolumab to potentially enable front-line development. |
Cohorts to evaluate every 3-week intravenous dosing and reduced hospitalization requirements are planned.
| 1 | Reference: Motzer RJ, et al. Final analysis of the TiNivo-2 phase 3 trial: Long-term outcome of Tivozanib (Tivo) in patients with metastatic renal cell carcinoma (mRCC). Poster presented at: ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL. Poster 34. Cross-trial comparison is provided for illustration only and is not based on head-to-head studies; trials differ in design, population and response assessment, and strong caution should be exercised when comparing data across unrelated trials. |
About XmAb819
XmAb819 is a potential first-in-class, tumor-targeted, T-cell engaging XmAb® 2+1 bispecific antibody in development for patients with clear cell renal cell carcinoma (ccRCC) and other tumors with high ENPP3 expression, including colorectal cancer, non-small cell lung cancer and papillary renal cell carcinoma. XmAb819 is designed to engage the immune system and to activate T cells for highly potent and targeted lysis of tumor cells expressing ENPP3. ENPP3 is a differentially expressed target, with high-level expression in renal cell carcinoma (RCC) and low-level expression on normal tissues. With two tumor-antigen binding domains and one T-cell binding domain, Xencor’s XmAb® 2+1 format is designed to enable antibodies to bind more avidly and selectively kill tumor cells with higher antigen density, potentially sparing normal cells. XmAb819 is being evaluated in a Phase 1 clinical study, and Xencor plans to initiate a potential registration-enabling study of XmAb819 as a monotherapy in advanced ccRCC by the end of 2027. Clinical development also includes evaluation of subcutaneous administration, combination therapy, and in additional ENPP3-expressing tumor types.
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About Xencor
Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and autoimmune diseases. More than 20 candidates engineered with Xencor’s XmAb® technology are in clinical development, and multiple XmAb medicines are marketed by partners. Xencor’s XmAb engineering technology enables small changes to a protein’s structure that result in new mechanisms of therapeutic action. For more information, please visit www.xencor.com.
Forward-Looking Statements
Certain statements contained in this press release may constitute forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include statements that are not purely statements of historical fact, and can generally be identified by the use of words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “indicates,” “supports,” and similar terms, or by express or implied discussions relating to Xencor’s business, including, but not limited to, statements regarding expectations for clinical progress, planned presentations of clinical data, planned and in process clinical trials, including trial design, timing for initiation or disclosing results, potential results, dose selection, expected results and discussions with regulatory authorities, Xencor’s cash runway, any potential accelerated approval or pathway, the potential for trials to be registrational, any potential approvals, the quotations from Xencor’s president and chief executive officer and the study investigator, and other statements that are not purely statements of historical fact. Such statements are made on the basis of the current beliefs, expectations, and assumptions of the management of Xencor and are subject to significant known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements and the timing of events to be materially different from those implied by such statements, and therefore these statements should not be read as guarantees of future performance or results. Such risks include, without limitation, the risks associated with the process of discovering, developing, manufacturing and commercializing drugs that are safe and effective for use as human therapeutics and other risks, including the ability of publicly disclosed preliminary clinical trial data to support continued clinical development and regulatory approval for specific treatments and the risks, uncertainties and other factors described under the heading “Risk Factors” in Xencor’s annual report on Form 10-K for the year ended December 31, 2025 as well as Xencor’s subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended to date. All forward-looking statements are qualified in their entirety by this cautionary statement and Xencor undertakes no obligation to revise or update these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.
Contacts
Charles
Liles
cliles@xencor.com
For media:
media@xencor.com
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