xncr-20240909
FALSE000132673200013267322024-09-092024-09-09

UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
___________________________________________________
FORM 8-K
___________________________________________________
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):  September 9, 2024
___________________________________________________
XENCOR, INC.
(Exact name of registrant as specified in its charter)
___________________________________________________
Delaware
001-3618220-1622502
(State or Other Jurisdiction of
Incorporation)
(Commission
File Number)
(IRS Employer
Identification Number)
465 North Halstead Street, Suite 200
PasadenaCalifornia
91107
(Address of Principal Executive Offices)
(Zip Code)
(626) 305-5900
(Registrant’s telephone number, including area code)
(Former name or former address, if changed since last report.)
___________________________________________________
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
Title of Each ClassTrading Symbol(s)Name of Each Exchange on Which Registered
Common Stock, par value $0.01 per shareXNCRNasdaq Global Market
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 o
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. o



Item 7.01. Regulation FD Disclosure.

On September 9, 2024, Xencor, Inc. (the “Company”) posted a presentation on the “Investors” section of the Company’s website (www.xencor.com), which includes descriptions of initial data from the ongoing Phase 1 dose-escalation study of XmAb819 (ENPP3 x CD3), descriptions of initial data from the ongoing Phase 1 dose-escalation study of XmAb808 (B7-H3 x CD28), and presentations of new programs to be developed for patients with autoimmune diseases and associated near-term clinical timelines. 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 September 9, 2024 and the Company disclaims any obligation to update 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 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, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.

Item 8.01. Other Events.

On September 9, 2024, , the Company issued a press release announcing clinical progress updates in early-stage oncology programs, XmAb819 (ENPP3 x CD3) and XmAb808 (B7-H3 x CD28), and XmAb drug candidates to be evaluated for the treatment of patients with autoimmune and inflammatory diseases, including plamotamab (CD20 x CD3), XmAb657 (CD19 x CD3), XmAb942 (Xtend™ TL1A) and the XmAb TL1A x IL-23 program. 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
99.2
104Cover Page Interactive Data File, formatted in Inline Extensible Business Reporting Language (iXBRL).
2


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: September 9, 2024
XENCOR, INC.
By:/s/ Celia Eckert
Celia Eckert
General Counsel & Corporate Secretary
3
xencorstrategycallandsep
® Xencor R&D Strategy Call September 9, 2024


 
2 Today’s Agenda Overview Rationale for bispecific antibodies in autoimmune & inflammatory diseases New pipeline programs: B-cell depleting T-cell engagers Plamotamab (CD20 x CD3) XmAb657 (CD19 x CD3) New pipeline programs: TL1A portfolio XmAb942 (Xtend TL1A) XmAb TL1A x IL-23 Potential first-in-class T-Cell engagers in solid tumor oncology XmAb819 (ENPP3 x CD3) XmAb808 (B7-H3 x CD28)


 
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, 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, as well as other risks described in Xencor's filings with the Securities and Exchange Commission. 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 of 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 “ ” 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.


 
4 • 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: 3 novel TCEs advancing in Phase 1 studies; narrow focus for vudalimab in mCRPC and 1L NSCLC • Autoimmune: Upcoming study initiation plans • 4Q’24: XmAb942 (Xtend TL1A) • 1H’25: Plamotamab (CD20xCD3) in RA • 2H’25: XmAb657 (CD19xCD3) • More than 15 technology license partnerships greatly broadens scope with little-to-no effort • Multiple commercialized XmAb antibodies ULTOMIRIS® MONJUVI®/MINJUVI® Proven Power of XmAb® Engineering: Proteins By Design® AstraZeneca Rare Disease Small changes, big functional impacts Advancing an optimized portfolio of XmAb drug candidates Partnerships leverage modular XmAb technology Registered trademarks: Ultomiris® (Alexion Pharmaceuticals, Inc.), Monjuvi® & Minjuvi® (Incyte Holdings Corp.) COLLABORATION PORTFOLIO INCLUDES XmAb Bispecific T-cell Engagers (TCEs) Xtend Antibodies with Potential Best-in-class Half-life Extension PLUG & PLAY TOOLKITS FOR RAPID PROTOTYPING RATIONALLY ENGINEERED XMAB DRUG CANDIDATES


 
5 World-leading protein engineers and proven XmAb® Fc platforms, supported by strong financial position of $585.0* million Experienced drug development team deliver rapid proof-of-concept clinical studies Rapidly prototype and optimize XmAb® drug candidates, designed with purpose to solve complex biological engineering problems Long-term potential benefit for patients through strict evaluation of data and competition to drive internal advancement towards commercialization or collaboration Xencor’s Disciplined Drug Development Strategy Validated Best-in-Class XmAb® Platforms Optimally Engineered Novel Drug Candidates Maximize Outcomes for All Stakeholders Focused Clinical Execution XmAb® Drug Development Model * As of 6/30/2024. Includes cash, cash equivalents & marketable debt. Updated 8/5/2024.


 
6 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 Ovarian cancer, oncology XmAb Program Undisclosed TCE Bispecific, Xtend Solid tumor oncology Solid Tumor Oncology: T-cell Selective, Dual Checkpoint Inhibitor Vudalimab PD-1 x CTLA-4 Bispecific, Xtend mCRPC 1L NSCLC Immunology Programs Plamotamab CD20 x CD3 Bispecific Rheumatoid Arthritis XmAb942 TL1A Xtend, FcKO Inflammatory Bowel Diseases (IBD) XmAb657 CD19 x CD3 2+1 Bispecific, Xtend Autoimmune Diseases XmAb Program TL1A x IL23 Bispecific, Xtend Autoimmune Diseases + chemotherapy Solid tumors Immunology + pembrolizumab +/- chemotherapy Key ccRCC clear cell renal cell carcinoma NSCLC non-small cell lung cancer mCRPC metastatic castration-resistant prostate cancer FcKO Fc knock out 1H’25 4Q’24 2H’25 Planned Study Initiation Next-Gen XmAb® Drug Design in Oncology & Autoimmune Diseases Pipeline focus on T-cell engagers and bispecific mechanisms


 
7 Rebalanced Portfolio Optimized for XmAb® Drug Development Validated targets across autoimmune disease, leveraging XmAb engineering Engineering Complexity Biological Uncertainty DiscontinuedNew Clinical Stage CD20 x CD3 Plamotamab Xtend TL1A XmAb942 Oncology CD28 TCEs PD1 x ICOS XmAb104 PD1 x CTLA4 Vudalimab Autoimmune Portfolio TL1A x IL23 Oncology CD3 TCEs Engineered Cytokines CD19 x CD3 XmAb657 CLDN6 x CD3 XmAb541 ENPP3 x CD3 XmAb819 IL12-Fc XmAb662 IL2-Fc (Treg) XmAb564 Key


 
8 ®Rationale for bispecific antibodies in autoimmune and inflammatory (A&I) diseases


 
9 ACCESSDOSINGMANUFACTURING REGULATORYPROOF OF CONCEPTSCIENTIFIC RATIONALE New Era Emerging for Bispecific Antibody Drug Development in Autoimmune and Inflammatory Diseases Recent clinical and academic studies have highlighted exciting clinical potential of both mechanisms Multiple related signaling pathways involved in A&I support dual inhibition (BsAbs) and depth of inhibition (TCEs) Recent U.S. FDA insight encourages BsAb development1 beyond oncology Efficient manufacturing process to produce one drug molecule versus multiple drugs in combination or cellular therapies Avoids complicated clinical dosing algorithms, with dual therapy and/or problematic co-formulation More favorable formulary access for a single drug product versus multiple drugs used in combination BsAb bispecific antibody TCE T-cell engager 1 “The agency has been encouraging drug development in this area. In 2021, FDA finalized a guidance on BsAb development programs.” (U.S. FDA, 2024)


 
10 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 demonstrated promise for patients with severe rheumatic and inflammatory autoimmune disorders in small academic studies, and depth of B-cell depletion has been linked to better clinical outcomes in larger randomized controlled trials Newly published data shows potential for multiple types of bispecific antibodies in autoimmune disease Nat Med. 2024 EULAR 2024 Front. Immunol. 2023 Lancet Gastroenterol Hepatol. 2023


 
11 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 & granzymes CD3ε Rheumatoid arthritis Multiple sclerosis Systemic lupus erythematosus ANCA-associated vasculitis Idiopathic inflammatory myopathy Myasthenia gravis NMOSD Pemphigus vulgaris Sjogren’s syndrome Systemic sclerosis 1 Schett G, et al. Ann Rheum Dis 2024;0:1-12.


 
12 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 share, with >$5bn in US sales reported during 202312 BENLYSTA US annual sales of >$1bn with high unmet need remaining for moderate-to-severe SLE12 B-cell depletion has demonstrated broad benefit across a wide-range of autoimmune diseases: ANCA-associated vasculitis5 Idiopathic inflammatory myopathy6 Myasthenia gravis7 NMOSD8 Pemphigus vulgaris9 Sjogren’s syndrome10 Systemic sclerosis11 ~2.2m Patients with RA in US by 20302 ~1.1m Patients with MS in US by 20303 >200k Patients with advanced SLE4 >700k Patients with other B-cell mediated diseases 1 Based on randomized controlled trials with positive primary endpoints (Schett G, et al. Ann Rheum Dis 2024;0:1–12. 2 J Manag Care Spec Pharm. 2018; 24(10):1010-1017. 3 JAMA Neurol. 2023; 80(7):693-701. 4 Arthritis Rheumatol. 2021 Jun; 73(6): 991–996. 5 J Clin Med. 2022;11(9):2573. 6 BMC Musculoskelet Disord. 2012; 13: 103. 7 Front Neurol. 2024; 15:1339167. 8 Mult Scler. 2024; 13524585231224683. 9 JAMA Dermatol. 2019; 155(5): 627-629. 10 Arthritis Care Res (Hoboken). 2017; 69(10):1612-1616. 11 J Manag Care Spec Pharm. 2020 Dec;26(12):1539-1547. 12 GlobalData.


 
13 ® Rheumatoid Arthritis: Where are we and where do we need to go? Roy Fleischmann, MD MACR Adjunct Professor of Medicine University of Texas Southwestern Medical Center Medical Director, Metroplex Clinical Research Center Dallas, Texas


 
14 *ACPA = anti-citrullinated protein antibody. Detected as anti-CCP Ab. Citrulline is a post-translational modification of arginine, e.g. at inflammatory sites Rituximab IL6 inhibitors Abatacept 2000s Methotrexate 1980s Gold 1930sAspirin 1898 Sulfasalazine 1940s TNF inhibitors 1998 JAK inhibitors 2012 ? 20?? New MoA PD-1? New JAK inhibitors? Molecular Degraders? CAR-Ts? T-Cell Engagers? Immunopathogenesis of Rheumatoid Arthritis


 
15 Rheumatoid Arthritis Manifestations • Systemic, inflammatory polyarthritis that leads to joint destruction, deformity, and loss of function. • Pathology involves synovial membranes and peri-articular structures of joints, typically resulting in uncontrolled inflammation with pannus formation and clinical symptoms of pain, swelling and stiffness which may lead to irreversible damage and deformity with functional limitation. Courtesy of S. Berney Eye scleritis keratoconjunctivitis Pleura effusions Lung fibrosis, nodules Lymph node reactive lymphadenopathies Pericardium effusions Spleen splenomegaly Kidney and gut amyloidosis Hematologic granulocytopenia hyperviscosity anemia thrombocytosis Muscle myopathy Dermatologic thinning, ulceration, Sjögren’s syndrome Nervous system peripheral neuropathy Cardiovascular atherosclerosis vasculitis Rheumatoid nodules Raynaud’s syndrome ACR Subcommittee on RA Guidelines. Arthritis Rheum. 2002;46:328; Goronzy JJ, Weyand CM. In: Klippel JH, et al, eds. Primer on the Rheumatic Diseases 2001; 12th ed. Atlanta, GA: Arthritis Foundation; 2001. p 209-16. Anderson RJ. ibid. 218; Arnett FC, et al. Arthritis Rheum. 1988;31:315


 
16 Even with the Most Effective Medications, 40% of RA Patients Do Not Reach Remission Even If They Continue with the Medication (AO) 0 20 40 60 80 100 SELECT-COMPARE: UPA + MTX vs ADA + MTX. Vertical line at Week 26 indicates the end of the PBO-controlled period. AO As Observed PBO placebo UPA Upadacitinib ADA adalimumab CDAI Clinical Disease Activity Index LDA low disease activity * CDAI remission is a stricter clinical metric than DAS28. Fleischmann R et al. EULAR 2023. Poster POS0849. 26 48 72 96 144 168 192120 216 240 264 Weeks CDAI* remission (≤2.8) CDAI LDA (≤10) 0 ADA continued (n=98)PBO to UPA (n=415) UPA continued (n=260) ADA to UPA (n=100) UPA to ADA (n=137) Pa tie nt s (% ) 0 20 40 60 80 100 26 48 72 96 144 168 1921200 216 240 264 Weeks Pa tie nt s (% ) 162/260 (62.3) 64/98 (65.3) 181/415 (43.6) 32/100 (32.0) 36/137 (75.2) What degree of disease activity can be reached with effective medications for RA?


 
17 RA patients have an increased risk of CV events1,2. Risk of CVD death 50% higher vs. general population, which correlates with CV risk factors and inflammation3,4. DMARDs reduce CV event risk5,6 if disease activity reduced7. Severe disease activity in RA patients is correlated with a 70-fold increased risk of developing malignant lymphomas, particularly diffuse large B cell lymphoma10. RA is associated with a 2-fold increased risk of SIE, thought to be due to defective immune system and comorbidities such as diabetes, pulmonary or renal disease and functional disability8. TNFα inhibitors increase the risk 2-fold and glucocorticoids 4-fold. Active RA is associated with a > 2-fold increase in the development of deep venous thrombosis and pulmonary embolus compared to the general population9. Consequences of Inadequately Treated RA Cardiovascular Disease (CVD) Serious Infection (SIE) Venous and Pulmonary Thrombosis Lymphoma 1 Avina-Zubieta JA, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008;59:1690-7. 2 Solomon DH, et al. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 2003; 107:1303-7. 3 Del Rincon I, et al. Escalante A. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 2002;48:1833-40. 4 Myasoedova E, et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis 2011;70:482-7. 5 Micha R, et al. Systematic review and metaanalysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol 2011;108:1362-70. 6 Barnabe C, et al. Systematic review and metaanalysis: anti-tumor necrosis factor a therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken) 2011;63:522-9. 7 Solomon DH, et al, Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events. Arthritis and Rheumatology. Vol. 67, No. 6, June 2015, pp 1449-55. 8 Listing J, et al. Rheumatology, 2013 52(1): 53-61. 9 Choi HK, et al. Ann Rheum Dis 2013;72:1182-87. 10 Baecklund E, et al. Arthritis Rheum 2006;54:692-701.


 
18 Unmet Needs in the Treatment of RA Current Landscape Trends • ~ 1,300,000 patients with RA in the US2 • This means that ~ 200,000 - 230,000 patients in the U.S. alone require new therapeutic options • We do not have the necessary tools to predetermine which patient will have a complete clinical response without adverse events to a specific mechanism or action or specific molecule. Survey of 25 rheumatologists1: What do they suspect will be the significant changes over the next 5 years in the treatment of RA? Convinced that bDMARDs and Jakinibs should be initiated earlier Emerging novel MoA offering improved efficacy, safety and tolerability Novel B-cell depleting therapies, CAR-T cell therapy, combination biologics, and more targeted, effective treatment options 1 Xencor survey of investigators 2 Helmick and Lawrence et al; Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15-25 of patients do not respond adequately or are unable to tolerate the currently approved medications1 ~15-18%


 
19 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 Upadacitinib 30 mg n=314 Upadacitinib 15 mg n=650 Adalimumab 40 mg n=327 Rituximab 2x1000mg n=170 Rituximab 2x1000mg n=308 Adalimumab 40 mg n=162 Tocilizumab 8mg/kg n=163 SELECT-EARLY SELECT-COMPARE (+MTX) SERENE (+MTX) REFLEX (+MTX) ADACTA Serious Infection Rate Median of Serious Infection Rate ACR Responses at Weeks 24 and 48 in TNF-IRs A REFLEX Study; Cohen S, et al. 2006 Arthritis Rheum 54(9): 2793-2806B) TNF-IR: TNF inhibitors Inadequate Responders; B Patients with up to 9.5 years of follow-up analyzed ≥2 years after any RTX treatment for limited return (LLN; <80 cells/μL) of CD19 B cells and CD19 cell counts below lower limit of quantification (LLQ; <20 cells/μL). CD19 cell counts were measured from peripheral blood; No measurements from other tissue compartments reported; van Vollenhoven, R.et al. 2015 J. Rheum. 42(10):1761-1766 C Cross-trial comparison of serious infection rates (24-week endpoint except for SELECT-COMPARE: 26 weeks). Clinical Experience of Rituximab in RA Week 24 Week 48 Rate of Serious Infection with Peripheral B-cell Depletion A % o f s er io us in fe ct io ns Rate of Serious Infection 32% 16% 3% 33% 8% 4% 63% 32% 15% 51% 34% 14% 0 10 20 30 40 50 60 70 80 90 100 ACR 20 ACR 50 ACR 70 ACR 20 ACR 50 ACR 70 % o f p at ie nt s Placebo + MTX† Rituximab + MTX‡ B C


 
20 New Therapies on the Horizon in RA JAK inhibitors Molecular degraders Potent B cell inhibitors Anti BLISS/APRIL T-Cell Engagers CAR-Ts PD-1 agonistsNeonatal Fc receptor inhibitors CD40 inhibitors


 
21 A Highly Effective Medication with a Risk Profile That Can Be Mitigated, Has a Very Favorable Benefit/Risk Profile for Patients with Rheumatoid Arthritis Benefit Risk Infection Malignancy Major adverse CV events Venous thrombosis Other adverse events Signs / symptoms Quality of life / function Prevent X-ray damage Work / home productivity Cost-efficacy Other factors Patient comorbidities Aggressiveness of disease Concomitant medications


 
22 ® New Pipeline Programs: B-cell Depleting T-cell Engagers Plamotamab (CD20 x CD3) XmAb657 (CD19 x CD3)


 
23 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 • Robust manufacturing process with high yield and excellent formulation stability data • N=154 from dose escalation and expansion cohorts with both IV and SC formulations in B-cell cancers • Comparable preliminary efficacy data to leading commercial CD20 x CD3 in patients with prior CAR-T • IV & SC dosing regimens with improved CRS data vs. leading commercial CD20 x CD31 • Existing inventories of drug product and drug substance for seamless integration into the next phase of clinical development Bispecific Fc Domain anti-CD3 scFv anti-CD20 Fab Planned proof-of-concept for the T-cell engager class in autoimmune and inflammatory disease BsAb bispecific antibody IV intravenous, SC subcutaneous NHP non-human primate CRS cytokine release syndrome 1 No head-to-head trial has been conducted evaluating plamotamab against other data included herein. Differences exist between clinical trial design, patient populations and the product candidates themselves, and caution should be exercised when comparing data across trials.


 
24 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 lin e) -7 0 7 14 21 28 0.0 0.2 0.4 0.6 0.8 1.0 1.2 Low dose High dose Day 0 (Predose) Day 4 Day 8 Day 30 0.0 0.5 1.0 1.5 2.0 2.5 B ce ll / T c el l ( C D 40 + / C D 8+ ) Low dose High dose


 
25 >95-99% Peripheral B-cell Depletion Observed in Lymphoma Patients with IV & SC Plamotamab in Phase 1 Monotherapy Study • Patients were identified (N=5) that had baseline absolute B-cell count > 30 cells/µL in the blood • >90% reductions in B-cell count also observed at lower doses Dose B -C el l L ev el R el at iv e to B as el in e Days Post Start of Treatment Relative Change in B-cell Count


 
26 Phase 1 Monotherapy Study of Plamotamab Heavily Pre-Treated Population with High Rates of Prior CAR-T Characteristics RD (IV) (n = 35) SC all cohorts (n = 20) Age, median (range) 69 (36-86) 67 (27-90) Baseline ECOG 0, n (%) 13 (37.1) 7 (35.0) 1 19 (54.3) 13 (65.0) 2 3 (8.6) 0 Bulky disease at study entry, n (%) > 6 cm 10 (28.6) 5 (25.0) > 10 cm 5 (14.3) 0 Median number of prior systemic therapies 4.0 (2-11) 4.0 (2-10) Refractory to last therapy, n (%) 25 (71.4) 10 (50.0) Prior transplantation, n (%) 3 (8.6) 4 (20.0) Prior CAR-T, n (%) 21 (60.0) 17 (85.0) RD (IV) recommended IV dose DLBCL diffuse large B-cell lymphoma HGBCL high-grade B-cell lymphoma ECOG Eastern Cooperative Oncology Group DLBCL + HGBCL Patient Characteristics


 
27 53% 44% 63% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Plamotamab SC Epcoritamab SC North America Epcoritamab SC Europe Epcoritamab SC ROW Plamotamab ORR Compared to Commercial CD20 x CD31 Regional differences in lymphoma prior therapy markedly impact outcomes 1 No head-to-head clinical trial has been conducted evaluating plamotamab against epcoritamab. Differences exist between trial design and patient populations, and caution should be exercised when comparing data across unrelated trials. 2 Thieblemont and Lugtenburg et al.; J Clin Oncol 41:2238-2247. Phase 1/2 expansion cohort of epcoritamab reported high variance in overall response rates (ORR) associated by treatment geography, with a significantly lower 44% ORR reported for North America due to high utilization of CAR-T (noted by study investigators), as compared to 62.7% ORR in Europe and 73.5% ORR in the rest of the world (ROW).2 Note: Plamotamab geographic enrollment distribution for the subcutaneous (SC) dosing cohort (n=17): 76.5% North America and 23.5% Europe. Overall Response Rate


 
28 No Grade 3 CRS and Lower Grade CRS Observed, Compared to Commercial CD20 x CD31 Epcoritamab SC CRS2Plamotamab SC CRS Pooled cohorts 1 No head-to-head clinical trial has been conducted evaluating plamotamab against epcoritamab. Differences exist between trial design and patient populations, and caution should be exercised when comparing data across unrelated trials. 2 Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell–Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial; Thieblemont and Lugtenburg et al.; J Clin Oncol 41:2238-2247. Data cutoff: January 31, 2022. 5 (25%) 1 (5%) 4 (22%) 1 (6%) 1 (8%) 2 (10%) 1 (5%) 0% 20% 40% 60% 80% 100% C1D1 n=20 C1D8 n=19 C1D15 n=18 C1D22 n=16 C2D1 n=13 C2D8 n=12 C2D15 n=13 C2D22 n=10 Pe rc en ta ge o f P at ie nt s w ith C R S Grade 2 Grade 1 4.5% 9.8% 27.2% 3.5% 1.5% 1.3% 2.0% 12.9% 1.4% 1.5% 2.7% 0.0% 20.0% 40.0% 60.0% 80.0% 100.0% Priming C1D1 0.16 mg n=157 Intermediate C1D8 0.8 mg n=153 First full C1D15 48 mg n=147 Second full C1D22 48 mg n=144 Third full+ C2D1+ 48 mg n=136 Pe rc en ta ge o f P at ie nt s w ith C R S Grade 3 Grade 2 Grade 1 No Grade 3 CRS Similar results across dose levels Summary of CRS at Recommended IV Dose regimen: < 50% incidence overall, no Grade 3, Cycle 1 limited


 
29 Plamotamab: Plan for Phase 1b/2a Rheumatoid Arthritis Study Start Maximal efficiency to clinical proof of concept in multi-drug resistant rheumatoid arthritis (MDR-RA) • 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 on a staggered start • Assess safety, biomarkers, initial efficacy in RA patients Plamotamab Control Phase 2a 24 week duration Phase 1b Dose regimen A Phase 1b/2a Study Initiation Planned for 1H’25 Dose regimen B Dose regimen … • Advance selected dosing regimen into placebo-controlled trial in MDR-RA patients • Single-cycle dosing in line with other B-cell depleting agents • 24-week efficacy endpoint with interim efficacy analysis at week 12 with paired biomarker assessment Single 1b/2a study for seamless transition to randomized proof-of-concept trial


 
30 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 • EULAR 2024 and subsequent updates of CD19 CAR-T clinical data highlighted potential issues with CAR-T approach on efficacy and safety • Rational design of XmAb657 supports best-in-class potential for clinical outcomes • Current timeline to FIH study in 2H’25 puts Xencor on-track to be a leading CD19 x CD3 program within autoimmune disease • High affinity and stability anti-CD19 binder • Bivalent to efficiently target B cells expressing very low levels of CD19 (e.g., plasma cells and plasmablasts) • Affinity-tuned and highly stable anti-CD3 binder • Uses Xencor’s clinically validated 2+1 format • Heterodimeric Fc domain engineered to abrogate effector function and improve half-life • Xtend Fc for long half life anti-CD3 1 scFv anti-CD19 2 Fabs Xtend


 
31 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 80 100 5000 10000 Days post administration B c el ls /μ L of b lo od 0 7 14 21 28 0 1 2 3 4 Days post administration % B c el ls a m on g ly m ph no de le uk oc yt es 0 7 14 21 28 0 1 2 3 4 5 Days post administration % B c el ls a m on g ly m ph no de le uk oc yt es 0 7 14 21 28 0 1 2 3 Days post administration % B c el ls a m on g bo ne m ar ro w le uk oc yt es Bone marrow Lymph nodes 0 7 14 21 28 0.0 0.5 1.0 1.5 2.0 Days post administration % B c el ls a m on g bo ne m ar ro w le uk oc yt es *peripheral B cells <1 B cell per µL; ‡this data point is zero B cells per µL ‡‡ ‡ B cells were gated as CD45+CD2-/lowCD20+CD4-CD8a-CD159a-


 
32 XmAb657: High IV Single DoseXmAb657: Low IV Single Dose Pre-dose Day -14 Study Day 8 Study Day 29 CD19+ 1x 5x 5x 5x1x 1x 1x 5x 5x 5x1x 1x Deep B-Cell Depletion in Lymph Nodes in NHPs Confirmed by CD19+ IHC Pre-dose Day -14 Study Day 8 Study Day 29 CD19+ CD19 IHC reagent antibody non-interfering with XmAb657


 
33 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 initiated • Further plans to investigate subcutaneous dosing and priming • First-in-human study planned to initiate in 2H’25 0 7 14 21 28 Time (Days post dose) Xm A b6 57 s er um c on c. [n g/ m L] , l og s ca le Long half life with Xtend Fc technology (~15 days in NHP) has potential for durable B-cell depletion 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 0 7 14 21 28 0.0 0.5 1.0 1.5 2.0 Days post administration % B c el ls a m on g bo ne m ar ro w le uk oc yt es Peripheral B cells Lymph node B cells


 
34 ® New Pipeline Programs: TL1A Portfolio XmAb942 (Xtend TL1A) XmAb TLA1 x IL-23


 
35 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 Two common forms: Crohn’s disease Ulcerative colitis Economic burden estimated at $5.4B in 20232 ~3m Estimated diagnoses in the US1 Significant Health Burden • Impaired quality of life • Lower life expectancy • Surgeries, hospitalization • Increased risk for intestinal resection • Increased risk for colorectal cancer Severe Symptoms of IBD • Fatigue • Fever • Reduced appetite • Mental health Current Standards of Care are Lacking S1P modulator 5-ASA Cortico- steroid α-TNF α-IL23 α-integrin JAK inhibitor Patients cycle through suboptimal treatments • Suboptimal efficacy: ~10-20% disease remission3 • Adverse events: Infection, malignancy, thromboembolism, cardiac • Burdensome regimens: poor patient compliance


 
36 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 RG6631 Phase 2 TUSCANY (Roche TL1A) (cross UC study comparison of Endoscopic Improvement)1 Xtend + FcKO Bispecific Fc Domain VEGA Ph2a (Clinical Remission of UC at Week 38)2 • Building upon proof-of-concept studies with TL1A targeted therapy and combination therapies for the treatment of Ulcerative Colitis (UC) and Crohn’s Disease (CD) • Validated best-in-class Xtend half-life extension in XmAb942 • First-in-class potential of TL1A x IL-23 to target dual pathway inhibition anti-TL1A 2 Fabs anti-TL1A 1 Fab anti-IL23 1 Fab 50% 64% 37% 28% 40% RG6631 (All Comers) RG6631 (Biomarker Positive) S1P Receptor Modulator Humira Entyvio 1 Sourced from Roivant presentation of TUSCANY, Entyvio (anti-integrin) and Humira (anti-TNF) data from VARSITY P3 study, S1P receptor modulator data from ELEVATE 52 P3 study 2 Guselkumab plus golimumab combination therapy versus guselkumab or golimumab monotherapy in patients with ulcerative colitis (VEGA); Feagan and Shao et al.; The Lancet G&H; Feb 2023 48% 31% 21% Combination (anti-TNF + anti- IL23) Guselkumab (anti-IL23) Golimumab (anti- TNF) (nominal p=<0.05)


 
37 Binding kinetics human & cyno TL1A Functional blockade (TF-1 apoptosis inhibition) Humanization, Biochemical evaluation, Developability assessments Functional assays, Immunogenicity risk assessment, NHP PK Nomination 25-50 8-10 XmAb lead + 3 alternates >1000 # of clones per stage Discovery Campaign for Anti-TL1A Generation Design of lead and backups in less than 6 months Recombinant human TL1A immunization of mice and rats Single B-cell antibody discovery


 
38 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-life extended >4X as compared to parental (71 days vs 15 days)2 Similar safety and immunogenicity risk as parental antibodies in studied antibodies using Xtend Fc domains3,4,5 Antibody thermostability maintained in studied antibodies using Xtend Fc domains6,7 Superior or comparable to other HLE technologies (e.g., YTE) across multiple studies and parameters6,7,8 Typical HLE scaling from cyno to human is ~3.5x9 Clinical Half-Life and Maintenance Dosing Ultomiris vs. Soliris10 Product Half-life (days)11 Dosing Interval1,12 Ultomiris (with Xtend ) 49.7-64.3 Q8W Soliris 11.33-12.1 Q2W 1 Ultomiris & Soliris drug labels 2 Ledgerwood Clin Exp Imm 2015 3 Lee et al. Blood 2019 4 Gaudinski et al. PLOS Med 2018 5 Vu et al. J Neurol 2023 6 Ko et al. Exp Mol Med 2022 7 Internal Data 8 Ko et al. Nature Letter 2014 9 Haraya & Tachibana. BioDrugs (2023) 37:99–108 10 Data adapted from FDA and EMA drug labels 11 Reported Half-life across approved indications 12 Maintenance dosing interval in adults Proprietary Xtend Fc Domain has been incorporated into ≥ 21 molecules that have been tested in clinical studies Xtend is commonly referred to as ‘LS’ in academic literature


 
39 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 >22 days supports Q8W to Q12W dosing in humans • High concentration formulation for subcutaneous dosing • First-in-human clinical studies to begin 4Q’24 Company Program1 Potent SC Dosing Q8-12W Dosing Half-life extension Low Immunogenicity Xencor XmAb942 Merck (Prometheus)2,3 MK-7240 Roche (Roivant)4,5 RG-6631 Sanofi (Teva)6 TEV-48574 TBD Predicted Discovery & characterization of XmAb942 accepted for presentation during UEG Week on Tues., Oct. 15 1 No head-to-head trial has been conducted evaluating XmAb942 against other data included herein. Differences exist between clinical trial design, patient populations and the product candidates themselves, and caution should be exercised when comparing data across trials 2 PRA023 Progress Update (Prometheus presentation) 3 Feagan et al. The Anti-TL1A Antibody PRA023 Demonstrated Proof-of-Concept in Crohn’s Disease: Phase 2a APOLLO-CD Study Results (DOP87) Abstract citation ID: jjac190.0127 4 Banfield et al. Br J Clin Pharmacol. 2020;86:812–824 5 Clarke et al. mAbs. 2018;10:4, 664-677 6 Danese et al. Clin Gastroenterology and Hepatology. 2021;19:11, 2324-32.e6


 
40 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 IL-23 Ab Control TL1A Ab Control TL1A x IL-23 Prototype 2 TL1A x IL-23 Prototype 1 0.0 01 0.0 1 0.1 1 10 10 0 0 5×103 1×104 1.5×10 4 2×104 2.5×10 4 Concentration (nM) R LU XmAb protein engineering allows for a range of stable molecular structures Prototype TL1A x IL-23p19 bispecifics are functionally active on both axes


 
41 Xencor Positioned for Best-in-Class TL1A Portfolio in $23bn+ Global IBD Market1 Tulisokibart2,3 ≈ 2027 IV Induction and Q4W Dosing with Less Potency1st RG66314,5 TEV-485746 XmAb942 (Xtend TL1A) XmAb® TL1A x IL23 Q4W Dosing and High Rate of Immunogenicity2nd Q8W+ SC Dosing with Leading PotencyBest-in-Class Next-Gen TL1A Timelines are illustrative only and subject to FDA approvals 1 Estimate of US, UK, Spain, Japan, Italy, Germany, France and Canada market size in 2030 (GlobalData) 2 PRA023 Progress Update (Prometheus presentation) 3 Feagan et al. The Anti-TL1A Antibody PRA023 Demonstrated Proof-of-Concept in Crohn’s Disease: Phase 2a APOLLO-CD Study Results (DOP87) Abstract citation ID: jjac190.0127 4 Banfield et al. Br J Clin Pharmacol. 2020;86:812–824 5 Clarke et al. mAbs. 2018;10:4, 664-677 6 Danese et al. Clin Gastroenterology and Hepatology. 2021;19:11, 2324-32.e6 2QW-4QW Dosing with Limited Efficacy Data in IBD3rd Dual-Blocked TL1A & IL-23 in Single Drug Product First-in-Class TL1A Bispecific Potential Commercializations for First-Gen Programs and XmAb® TL1A Portfolio


 
42 ®Potential First-in-Class T-Cell Engagers in Solid Tumor Oncology


 
43 XmAb® T-Cell Engager Programs Designed to Address Unmet Need with Potential Across Multiple Tumor Types XmAb819 (ENPP3 x CD3) • Engineered for greater selectivity for ENPP3- expressing tumor cells compared to normal cells, which also express ENPP3 at lower levels • In development for patients with relapsed/ refractory clear cell RCC (ccRCC), which has nearly uniformly high ENPP3 expression • Dose-escalation ongoing XmAb541 (CLDN6 x CD3) • Engineered for CLDN6 selectivity over similar CLDN9, CLDN3 and CLDN4 • In development for patients with CLDN6+ tumors, including ovarian cancer • Dose-escalation ongoing XmAb808 (B7-H3 x CD28) • Engineered to provide tumor-selective co-stimulation only when bound to tumor cells • Combination with anti-PD1 (pembrolizumab) • In development for patients with solid tumors • Dose-escalation ongoing anti-CD3 1 scFv anti-ENPP3 2 Fabs Bispecific Fc Domain anti-CD3 1 scFv anti-CLDN6 2 Fabs Xtend anti-CD28 1 Fab anti-B7-H3 2 Fabs XtendBispecific Fc Domain Bispecific Fc Domain


 
44 XmAb819 Status Update1: Encouraging Initial Data in Ongoing Dose Escalation in ccRCC XmAb819 Potential first-in-class ENPP3 x CD3 Dose escalation on-track with RECIST responses in recent dose cohorts >$2bn peak sales potential in ccRCC2 1 Update provided 09-Sep-2024, based on 30-Aug-2024 data cutoff 2 Based upon internal Xencor projections of non-risk adjusted peak sales ccRCC clear cell renal cell carcinoma MTD maximum tolerated dose Observed in escalation: • Clear initial evidence of anti-tumor activity, including RECIST responses, in recent cohorts • Duration of treatment for several patients in earlier dose cohorts has extended beyond one year • Cytokine release syndrome (CRS) manageable • No MTD reached; tolerability from recent dose cohorts continues to support dose escalation XmAb819 remains on-track to reach target dose levels by year-end • Investigators remain highly engaged, and enrollment into new dose cohorts has been rapid • Intravenous and subcutaneous cohorts continue dose escalation in parallel • Evaluation of expansion into additional tumor types is ongoing • Clinical update and first dose expansion cohort expected to start during 1H’25


 
45 XmAb808 Status Update1: Continued Progress in Dose Escalation Observed in escalation: • Tolerability from recent dose cohorts remains supportive of continued combination with per label dosing of pembrolizumab • Safety data have supported adding cohorts with Day 1 start for dosing the combination of XmAb808 and pembrolizumab, along with cohorts that use a four-week XmAb808 monotherapy run-in period • Dose-escalation cohorts continue to enroll patients with multiple tumor types, majority with mCRPC • For the subgroup of mCRPC patients, biologic activity of XmAb808 has been observed with PSA declines during the four-week monotherapy run-in period, but higher doses are expected to be needed to trigger more meaningful clinical activity • Clinical update and dose expansion expected to start during 1H’25 XmAb808 Potential first-in-class B7-H3 x CD28 Dose escalation on-track with PSA reductions observed for patients with mCRPC during monotherapy run-in period >$3bn peak sales potential2 1 Update provided 09-Sep-2024, based on 16-Aug-2024 data cutoff 2 Based upon internal Xencor projections of non-risk adjusted peak sales mCRPC metastatic castration-resistant prostate cancer XmAb808 remains on-track to reach target dose levels by year-end


 
46 Guidance for Progress Across XmAb® Portfolio Programs in 2024 XmAb942 Xtend TL1A Present preclinical data during UEG Week 2024 on October 15 XmAb541 CLDN6 x CD3 Dose first patient during 1H 2024, enroll Phase 1 study Initiate first-in-human Phase 1 study in Q4 2024 XmAb Drug Candidate 2024 Priority Solid Tumors: T-Cell Engagers (CD3 & CD28) Immunology  XmAb819 ENPP3 x CD3 Advance dose escalation toward target dose levels in 2024 XmAb808 B7-H3 x CD28 Advance dose escalation toward target dose levels in 2024 Plamotamab CD20 x CD3 Define clinical development plan XmAb657 CD19 x CD3 GMP campaign and IND preparation  


 
47 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 CD3 Advance toward target dose levels Mono & combo cohort expansion readout Evaluate chemo combination safety XmAb942 Xtend TL1A IBD+ SAD readout MAD readout and Phase 2 start Plamotamab CD20 x CD3 Rheumatoid arthritis Initiate Phase 1/2 study XmAb657 CD19 x CD3 Autoimmune Initiate FIH study 1H’25 2H’25 Immunology Portfolio SAD Single ascending dose MAD multiple ascending dose FIH first-in-human


 
® Xencor R&D Strategy Call September 9, 2024


 
Document

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Xencor Announces XmAb Drug Candidates in Autoimmune Disease with Near-Term Clinical Plans and Shares Clinical Progress in Early-Stage Oncology Programs
-- Phase 1 healthy volunteer study of half-life extended anti-TL1A antibody XmAb942 to dose first subject in Q4 2024, with data anticipated in the first half of 2025 --
-- XmAb® T-cell engagers plamotamab (CD20 x CD3) and XmAb657 (CD19 x CD3) to be evaluated in autoimmune diseases, with respective Phase 1b/2a and Phase 1 studies to initiate in 2025 --
-- Ongoing Phase 1 dose escalation of XmAb819 (ENPP3 x CD3) in advanced clear cell renal cell carcinoma shows initial encouraging clinical activity including RECIST responses --
-- Management hosting webcast and conference call at 8:00 a.m. ET / 5:00 a.m. PT Today --
PASADENA, Calif.-- Sep. 9, 2024-- Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, today announced four new XmAb® programs in development for the treatment of patients with autoimmune diseases and provided updates from dose-escalation studies evaluating its first-in-class oncology programs, including XmAb819 (ENPP3 x CD3) in patients with advanced clear cell renal cell carcinoma and XmAb808 (B7-H3 x CD28) in patients with advanced solid tumors.
“Xencor’s clinical pipeline of XmAb bispecific T-cell engagers and newly announced autoimmune programs have multiple near-term milestones and offer a balance of opportunities to deliver novel treatment options that could potentially make a real difference in patients’ lives. The foundation of our portfolio is world-class protein engineering, using our XmAb platforms to potentially solve complex engineering problems and rationally build drug candidates that address specific clinical opportunities,” said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. “Our goal is clear—fully leverage our protein engineering strengths and reduce exposure to biological uncertainties to increase our overall opportunities for clinical success.”
Clinical Progress Updates in Early-Stage Oncology Programs: XmAb819 (ENPP3 x CD3) and XmAb808 (B7-H3 x CD28)
XmAb819: ENPP3 x CD3 bispecific T-cell engager in Phase 1 dose escalation for patients with advanced clear-cell renal cell carcinoma (ccRCC)
XmAb819 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing ENPP3, an antigen highly expressed on kidney cancers. Xencor’s XmAb 2+1 multivalent format used in XmAb819 enables greater selectivity of ENPP3-expressing tumor cells compared to normal cells, which express lower levels of ENPP3.
Clinical update: Initial evidence of anti-tumor activity has been observed in recent dose-escalation cohorts in the ongoing Phase 1 study, including RECIST responses, and the duration of treatment for several patients in earlier dose cohorts has extended beyond one year. Cytokine release syndrome remains manageable, and the tolerability profile from recent dose cohorts, including no maximum tolerated dose being reached, supports continued dose escalation toward target dose levels.
Guidance: The Company continues to anticipate reaching target dose levels by year end and plans to provide a clinical update around initiation of the first dose expansion cohort during the first half of 2025.



XmAb808: B7-H3 x CD28 bispecific T-cell engager in Phase 1 dose escalation in advanced solid tumors
XmAb808 is a tumor-selective, co-stimulatory CD28 bispecific antibody that binds to the broadly expressed tumor antigen B7-H3 and is constructed with the XmAb 2+1 format. Co-stimulation is required for T cells to achieve full activation, and targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells when the antibodies are bound to tumor cells.
Clinical update: The majority of patients enrolled into the ongoing Phase 1 dose-escalation study are men with metastatic castration-resistant prostate cancer (mCRPC). In this group of patients, prostate specific antigen (PSA) declines have been observed during the four-week monotherapy safety run-in period. Tolerability from recent dose cohorts remains supportive of continued dose escalation in combination with pembrolizumab.
Guidance: The Company continues to anticipate reaching target dose levels by year end and plans to provide a clinical update around initiation of dose expansion cohorts during the first half of 2025.
XmAb Drug Candidates for the Treatment of Patients with Autoimmune and Inflammatory Diseases and Planned Clinical Studies: Plamotamab (CD20 x CD3), XmAb657 (CD19 x CD3), XmAb942 (Xtend™ TL1A) and the XmAb TL1A x IL-23 Program
Plamotamab: CD20 x CD3 bispecific T-cell engager to be evaluated in patients with multi-drug resistant rheumatoid arthritis (MDR-RA), with Phase 1b/2a study anticipated to initiate in the first half of 2025
Xencor plans to initiate a Phase 1b/2a proof-of-concept study for plamotamab in MDR-RA in the first half of 2025. The Phase 1b portion of the study will select a priming and step-up dose regimen based on the regimen established in oncology, and will assess the initial safety, efficacy, and biomarkers of plamotamab in patients with MDR-RA. The selected dose regimen will then be evaluated in the randomized Phase 2a portion, with efficacy determined at week 24.
Xencor previously completed a Phase 1 clinical study of plamotamab in hematologic cancers, completing enrollment in late 2023. Results from the study showed favorable tolerability and comparable preliminary efficacy data, when cross compared to results from studies of a competitor molecule within the class, with similar patient baseline characteristics. Based on these clinical outcomes, significant B-cell depletion observed in preclinical studies, and the emergent biology supportive of B-cell targeted T cell engagers for the treatment of patients with autoimmune diseases, Xencor plans to evaluate plamotamab in MDR-RA, in which patients progressed through two prior lines of therapy.
XmAb657: Rationally designed CD19 x CD3 bispecific T-cell engager for patients with autoimmune diseases, with first-in-human Phase 1 study anticipated to initiate in the second half of 2025
Xencor has leveraged its XmAb protein engineering platforms to create XmAb657, a potent, potentially long-acting CD19 x CD3 bispecific antibody, utilizing the XmAb 2+1 bispecific antibody format and Xtend™ Fc technology. In non-human primate studies, a single dose of XmAb657 deeply reduced B cells by over 99.98% in the peripheral compartment, bone marrow and lymph nodes, which was sustained for at least 28 days. Half-life was estimated to be 15 days, which indicates a potential for durable B-cell depletion in clinical studies. XmAb657 was well tolerated preclinically, with no clinical signs of cytokine release syndrome. Xencor plans to initiate a first-in-human study during the second half of 2025.
XmAb942: A novel high-affinity anti-TL1A antibody designed for extended half-life, under development for the treatment of inflammatory bowel diseases (IBD), with first-in-human Phase 1 study anticipated to initiate in the fourth quarter 2024



XmAb942 is a monospecific anti-TL1A antibody, utilizing Xencor’s Xtend Fc domain and proprietary Fc silencing technology, with potentially class-leading potency, and is under development for patients with IBD. The two most common forms of IBD are Crohn’s disease and ulcerative colitis. Half-life preclinically was greater than 22 days, potentially supporting an 8- to 12-week dosing regimen in humans. An abstract with preclinical characterization was accepted for presentation at the United Europe Gastroenterology Week (UEGW) in Vienna, Austria on Tuesday, October 15. Xencor anticipates dosing the first subject in a first-in-human, single-ascending dose study of XmAb942 in the fourth quarter of 2024, with interim data during the first half of 2025.
XmAb TL1A x IL-23 Program: Potential first-in-class bispecific antibody to combine two validated biological pathways of interest into one drug candidate for the treatment of IBD, leveraging Xencor’s world-class protein engineering
An expertly engineered XmAb TL1A x IL-23p19 bispecific antibody could potentially provide dual targeting of important inflammatory pathways for autoimmune and inflammatory disease, while avoiding the complexities of dosing and formulary access for two separate TL1A and IL23 targeted drugs. Xencor anticipates initiating first-in-human studies during 2026.
Conference Call and Webcast
Xencor will host a conference call and webcast today at 8:00 a.m. ET (5:00 a.m. PT) to review the topics outlined in this news release.
The live webcast may be accessed through “Events & Presentations” in the Investors section of the Company’s website, located at investors.xencor.com. Telephone participants may register to receive a dial-in number and unique passcode that can be used to access the conference call. A recording will be available for at least 30 days.
About Xencor
Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and other serious 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 proteins 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,” 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, new XmAb candidates and programs, planned and in process clinical trials, the quotations from Xencor's president and chief executive officer, 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, in each case as described in



Xencor's public securities filings. For a discussion of these and other factors, please refer to Xencor's annual report on Form 10-K for the year ended December 31, 2023 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 this press release to reflect events or circumstances after the date hereof, except as required by law.
Contacts
For Investors:
Charles Liles
cliles@xencor.com
(626) 737-8118
For Media:
Cassidy McClain
Inizio Evoke
cassidy.mcclain@inizioevoke.com
(619) 694-6291