Xencor Stock

Xencor, Inc. (Xencor) operates as a clinical-stage biopharmaceutical company.

The company is focused on discovering and developing engineered antibody therapeutics to treat patients with cancer and other serious diseases, who have unmet medical needs. The company uses its protein engineering capabilities to increase its understanding of protein structures and interactions and to design new technologies and XmAb drug candidates with improved properties. The company advances these candidates into clinical-stage development, where the company is conducting Phase 1 and Phase 2 studies for a broad portfolio of programs, to determine which programs the company advances into later stages of development and potentially commercialization, which programs the company partners to access complementary resources to optimize development, and which programs the company terminate.

The company's approach to protein design includes engineering Fc domains, the parts of antibodies that interact with multiple segments of the immune system and control antibody structure. The Fc domain is constant and interchangeable among antibodies, and the company's engineered XmAb Fc domains can be readily substituted for natural Fc domains.

The company's protein engineering capabilities and Fc technologies enable the company and its partners to develop XmAb antibodies and other types of biotherapeutic drug candidates with improved properties and functionality, which can provide innovative approaches to treating disease and potential clinical advantage over other treatment options. For example, the company has developed an antibody scaffold to rapidly create novel multi-specific antibodies that bind two or more different targets simultaneously, creating entirely new biological mechanisms. Other applications of the company's protein engineering technologies enhance antibody performance by increasing immune inhibitory activity, improving cytotoxicity, extending circulating half-life and stabilizing novel protein structures, such as engineered cytokines. Three marketed XmAb medicines have been developed with the company's protein engineering technologies.

The company's protein engineering capabilities allow the company to continually explore new functionality in the Fc region, which provides the company with opportunities to create new technology platforms; engineer new drug candidates to advance into development or as partnering opportunities; and provide collaboration and licensing opportunities with partners for application of the company's technologies, access to its technologies, access to the company's drug candidates, or combinations of each.

Strategy

The key elements of the company's strategy are to advance the development of its XmAb antibody programs for oncology and other serious diseases; build and manage a diversified portfolio of XmAb drug candidates; leverage the company's protein engineering capabilities, XmAb Fc domains, and XmAb drug candidates with partnerships, collaborations, and licenses to generate revenue streams, create new drug candidates and combination treatments, and identify new indications for the company's pipeline of drug candidates (such as generate revenue streams, create new XmAb drug candidates and investigate novel combination therapies, and identify new indications for the company's pipeline of drug candidates); broaden the functionality of the company's XmAb Fc technology platforms; and continue to expand the company's patent portfolio protecting its Fc technologies and XmAb drug candidates.

XmAb Bispecific Fc Domain and New Multi-Specific Antibody Formats

The company's modular approach to protein engineering is a distinguishing feature of the company's Fc technologies. This inherent flexibility enables the company to design multiple XmAb drug candidates with distinct and novel mechanisms-of-action and to seek out new applications of the XmAb Bispecific Fc Domain. The company's business, research, and clinical efforts are to develop and advance its Fc technologies and the company's portfolio of XmAb drug candidates in oncology and other serious diseases.

CD3 Candidates

The company has significantly expanded the potential of its CD3 T cell engagers with the multi-specific XmAb 2+1 bispecific antibody format, utilizing two identical tumor targeting domains and one CD3 targeting domain. The affinities for antigen binding are engineered to enable selective engagement and killing of high antigen-expressing tumor cells over low antigen-expressing normal cells. In preclinical models, XmAb 2+1 bispecific antibodies bound preferentially to tumor cells compared to normal cells and effectively recruited T cells to kill tumor cells selectively. These properties will be particularly important when developing bispecific antibodies against many solid tumor targets, where standard monovalent targeting of tumor antigens could lead to poor tolerability because such targets are often expressed on a range of normal tissues, including critical organs. The company's XmAb819 and XmAb541 CD3 candidates have been designed using the company's CD3 2+1 format.

CD28 Candidates

The company's XmAb808 CD28 candidate has been engineered to provide selective CD28 co-stimulation of T cells, activating them when bound to tumor cells.

TME Activator Candidate

The company's tumor microenvironment (TME) activator candidate, vudalimab, has been designed to promote tumor-selective T-cell activation by targeting multiple checkpoints. Vudalimab also incorporates the company's Xtend technology for longer half-life.

Cytokine Candidates

The company's engineered novel cytokine candidates are fusions of XmAb Bispecific Fc Domains and immune signaling proteins. The company's cytokine candidates efbalropendekin alfa (XmAb306), XmAb564 and XmAb662 have been designed with reduced potency to improve therapeutic index and with the company's Xtend technology for longer half-life.

The company continues to invest in its protein engineering efforts to identify novel technologies and drug candidates.

Other XmAb Fc Domains

The company has also created additional XmAb Fc domains, and the company has successfully entered partnerships for these technologies and for XmAb drug candidates that incorporate them. The company continues to seek additional partnering and licensing opportunities for these Fc domains. Additional XmAb Fc domains include:

Immune Inhibitor Fc Domain - selective immune inhibition and rapid target clearance, targeting the receptor FcgammaRIIb;

Cytotoxic Fc Domain - increased cytotoxicity, targeting the receptors FcgammaRIIIa on natural killer (NK) cells and FcgammaRIIa on other immune system cells; and

Xtend Fc Domain - extended antibody half-life, targeting the receptor FcRn on endothelial cells.

Approved or Authorized Medicines Engineered with XmAb Fc Domains

Three medicines that have been developed with the company's XmAb Fc domains are now marketed or made available by the company's partners.

Sotrovimab: Vir Biotechnology, Inc. and its partner GSK have made available sotrovimab, an antibody that targets the SARS-CoV-2 virus, which in May 2021 received an emergency use authorization (EUA) from the United States Food and Drug Administration (FDA) for the early treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and at high risk for progression to severe COVID-19, including hospitalization or death. In March 2022, the FDA deauthorized sotrovimab's use in all U.S. regions due to increases in the proportion of COVID-19 cases caused by the Omicron BA.2 subvariant. Sotrovimab has obtained emergency authorization, temporary authorization or marketing approval (under the brand name Xevudy) for early treatment of COVID-19 in more than 30 countries. Sotrovimab incorporates the company's Xtend Fc domain for longer duration of action. Xevudy is a registered trademark of GSK.

Ultomiris (ravulizumab-cwvz): Alexion's Ultomiris is approved in the U.S., Europe, and Japan for the treatment of certain patients with paroxysmal nocturnal hemoglobinuria (PNH), certain patients with atypical hemolytic uremic syndrome (aHUS) and certain patients with generalized myasthenia gravis (gMG). In May 2023, Ultomiris was approved in the EU and Japan for the treatment of certain adult patients with neuromyelitis optica spectrum disorder (NMOSD). Alexion is also evaluating Ultomiris in a broad late-stage development program across additional hematology and neurology indications. Alexion used the company's Xtend Fc Domain to enhance the half-life of Ultomiris to allow for a longer duration of action, less frequent dosing and reduced patient burden of therapy compared to the previous generation therapy, Soliris.

Monjuvi (tafasitamab-cxix): In 2020, the FDA approved Monjuvi under accelerated approval. Monjuvi is a humanized Fc-modified CD19 targeting immunotherapy indicated in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). In August 2021, the European Commission granted conditional marketing authorization for Minjuvi (tafasitamab) in combination with lenalidomide, followed by tafasitamab monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplantation (ASCT). In addition to its approved indication, tafasitamab is being evaluated as a therapeutic option in ongoing pivotal trials for first-line DLBCL, relapsed or refractory follicular lymphoma (FL) and relapsed or refractory marginal zone lymphoma (MZL). Tafasitamab was created and initially developed by the company. Tafasitamab is marketed by Incyte under the brand name Monjuvi in the U.S. and under the brand name Minjuvi in Europe and Canada. Monjuvi and Minjuvi are registered trademarks of Incyte.

Drug Candidates in Clinical Development

There are 22 clinical-stage drug candidates or marketed medicines that have been developed with one or more of the company's XmAb technologies.

A partner is also advancing a drug candidate that incorporates the company's DN-TNF technology.

The company is also supporting an investigator sponsored trial evaluating vibecotamab (CD123 x CD3).

The company regularly evaluates its portfolio of candidates and make additional investments in candidates with promising early-stage clinical data, partner out other candidates, and stop development of candidates where early clinical data does not support further investment by the company. During 2023:

The company initiated a Phase 1b/2 study of vudalimab in combination with chemotherapy, as a first-line treatment in patients with advanced non-small cell lung cancer;

The company initiated a Phase 1 study for its XmAb662 program;

The company submitted an investigational new drug (IND) application for its XmAb541 program; and

The company stopped development of the XmAb104 program, and the company also closed gynecologic tumor cohorts in the Phase 2 vudalimab monotherapy study due to the rapidly changing competitive environment in these indications.

XmAb Bispecific Antibody Drug Candidates in Clinical Development

10 XmAb bispecific antibody drug candidates are in active clinical development internally or with the company's partners:

Three candidates are wholly owned and are being evaluated by the company in Phase 2 or Phase 1 studies; one wholly owned candidate has an open IND and is pending Phase 1 study initiation;

One candidate is being co-developed with partners; and

Five additional candidates are being advanced by partners.

Additional candidates are advancing through the preclinical stages of development. XmAb bispecific antibody drug candidates in clinical development include:

Wholly Owned Development Candidates

Vudalimab is a bispecific antibody that targets PD-1 and CTLA-4, two immune checkpoint receptors, and is designed to promote tumor-selective T-cell activation. Data from a Phase 1 study that enrolled heavily pretreated patients with multiple solid tumor types indicated that vudalimab was generally well-tolerated with encouraging clinical activity. The company continues to develop vudalimab for patients with metastatic castration-resistant prostate cancer (mCRPC) and patients with locally advanced or metastatic non-small cell lung cancer. The company is conducting two Phase 2 clinical studies of vudalimab in patients with mCRPC, a study of vudalimab as a monotherapy in the clinically defined high-risk patient population and a study of vudalimab in combination with chemotherapy, in the aggressive variant patient population. In the Phase 2 monotherapy study, vudalimab has been generally well tolerated and associated with response to treatment in multiple patients who have visceral or lymph node metastases. The company is also conducting a Phase 1b/2 study evaluating vudalimab as a first-line treatment in patients with locally advanced or metastatic non-small cell lung cancer.

XmAb819 is a first-in-class ENPP3 x CD3 XmAb 2+1 bispecific antibody that the company is developing for patients with renal cell carcinoma (RCC). The XmAb 2+1 multivalent format enables greater selectivity for ENPP3 expressing tumor cells compared to normal cells, which also express ENPP3 at lower levels. The company is conducting a Phase 1 study evaluating XmAb819 in patients with advanced clear cell RCC.

XmAb808 is a tumor-selective, co-stimulatory XmAb 2+1 bispecific antibody designed to bind to the broadly expressed tumor antigen B7-H3, and selectively to the CD28 T-cell co-receptor only when bound to tumor cells, which was demonstrated in in vitro studies. In vivo studies further demonstrated strong potentiation of checkpoint and CD3 cytotoxic activity. The company is conducting a Phase 1 study of XmAb808 in combination with pembrolizumab in patients with advanced solid tumors.

XmAb541 is a Claudin-6 (CLDN6) x CD3 XmAb 2+1 bispecific antibody that the company is developing for patients with ovarian cancer and other solid tumor types. The XmAb 2+1 multivalent format enables greater selectivity for CLDN6 over similar Claudin family members, such as CLDN9, CLDN3 and CLDN4. The investigational new drug (IND) application for XmAb541 has been allowed to proceed by the FDA, and the company plans to initiate a Phase 1 study in the first half of 2024.

Candidates Co-Developed with Partners

Plamotamab is a bispecific antibody that targets CD20, an antigen on B-cell tumors, and CD3, an activating receptor on T cells. In October 2021, the company entered into a global collaboration and license agreement with Janssen Biotech, Inc. (Janssen), a Johnson & Johnson company, to advance plamotamab and XmAb CD28 bispecific antibody combinations for the treatment of patients with B-cell malignancies (2021 J&J collaboration). J&J received worldwide exclusive development and commercial rights to plamotamab, and the company is collaborating with J&J on further clinical development of plamotamab. The company conducted a Phase 1 study of plamotamab in patients with non-Hodgkin's lymphomas. Results from the expansion portion of the study indicate that intravenous plamotamab monotherapy was well tolerated and demonstrated encouraging clinical activity in heavily pretreated patients at the recommended Phase 2 intravenous dose. In 2023, the company completed enrolling patients in subcutaneous dose escalation cohorts of this study.

Candidates Advanced by Partners

Xaluritamig (AMG 509) is a STEAP1 x CD3 2+1 bispecific antibody that the company's partner Amgen is advancing for the treatment of patients with prostate cancer. The XmAb 2+1 multivalent format enables higher binding capability for STEAP1 expressing cells. Amgen is completing patient enrollment in the dose expansion portion of a Phase 1 study of xaluritamig in patients with mCRPC. In October 2023, at the European Society for Medical Oncology (ESMO) Congress, encouraging interim clinical results from the study were presented during an oral proffered paper session, validating the potential of the XmAb 2+1 format. Amgen is planning two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer.

ASP2138 is a Claudin-18.2 x CD3 2+1 bispecific antibody that the company's partner Astellas is advancing for the treatment of patients with gastric, gastroesophageal and pancreatic cancers and is being evaluated in a Phase 1 study. The XmAb 2+1 multivalent format enables higher binding capability for Claudin-18.2 expressing cells.

JNJ-9401 is a PSMA x CD28 bispecific antibody that J&J is advancing for the treatment of patients with prostate cancer and is being evaluated in a Phase 1 study. JNJ-9401 was developed with J&J under the company's 2020 collaboration.

JNJ-1493 is a B-cell x CD28 bispecific antibody that J&J is advancing for the treatment of patients with B-cell malignancies and is being evaluated in a Phase 1 study. JNJ-1493 was developed with J&J under the company's 2021 collaboration.

Novartis XmAb undisclosed antibody candidate. Novartis is evaluating an undisclosed antibody drug candidate that was developed with the company's bispecific Fc technology under the company's collaboration with them.

Cytokine Drug Candidates in Clinical Development

3 XmAb cytokine drug candidates are in active clinical development internally or with the company's partners, which include:

Efbalropendekin alfa (XmAb306/RG6323) is a potency-reduced IL15/IL15-receptor alpha complex fused to the company's bispecific Fc domain (IL15/IL15Ra-Fc). The company is co-developing the program in collaboration with Genentech, a member of the Roche Group. Genentech is conducting a Phase 1 study of XmAb306 as a single agent and in combination with atezolizumab in patients with advanced solid tumors and is also conducting Phase 1 studies, evaluating XmAb306 in patients with relapsed/refractory multiple myeloma, either in combination with daratumumab (anti-CD38 antibody) or in combination with cevostamab (FcRH5 x CD3 bispecific antibody). Pursuant to the terms of the amended agreement with Genentech, effective June 1, 2024, Genentech will assume sole responsibility over all clinical, regulatory and commercial activities.

XmAb564 is a monovalent, potency-reduced interleukin-2 Fc (IL-2-Fc) fusion protein, engineered to selectively activate and expand regulatory T cells (Tregs) for the potential treatment of patients with autoimmune diseases. XmAb564 is engineered with reduced binding affinity for IL-2's beta receptor and increased binding affinity for its alpha receptor. In a Phase 1a clinical study of XmAb564, a single dose of XmAb564, administered subcutaneously in healthy volunteers, was well tolerated and generated durable, dose-dependent and selective expansion of Tregs. The company has been conducting a randomized, double-blind, placebo-controlled Phase 1b clinical study to evaluate the safety and tolerability of multiple ascending doses of XmAb564, administered subcutaneously in patients with atopic dermatitis or psoriasis. The company plans to conclude the Phase 1b study in the first half of 2024 and pause further development of XmAb564 until after assessment of future data from competitor programs in this class and review of safety and biomarker data in the Phase 1b study.

XmAb662 is a potency-reduced interleukin-12 Fc (IL12-Fc) fusion protein engineered to increase anti-tumor activity and immunogenicity in the tumor microenvironment by promoting high levels of interferon gamma secretion from T cells and NK cells. In preclinical testing, the company's engineered IL12-Fc fusions demonstrated an improved pharmacokinetic profile and therapeutic window compared to a native IL12-Fc fusion, with superior exposure, a more gradual dose response and more sustained interferon gamma response. XmAb662 demonstrated significant anti-tumor activity, along with increases in NK cells, T cells, serum IP-10 and interferon gamma, which were further enhanced when combined with an anti-PD-1 antibody. The company has been conducting a Phase 1 study to evaluate XmAb662 in patients with advanced solid tumors. The company plans to conclude the Phase 1 study in the first half of 2024 and pause further development of XmAb662 until after assessment of future data from competitor programs in this class and review of safety and biomarker data in the Phase 1 study.

Xtend and Cytotoxic Fc Drug Candidates in Clinical Development

Two drugs engineered with the company's Xtend Fc Domain and one drug the company engineered with its XmAb Cytotoxic Fc Domain are marketed commercially by partners. In addition to these approved drugs, the company's partners are advancing multiple clinical-stage programs with antibodies engineered with Xtend and/or Cytotoxic Fc Domains, including:

Vir Biotechnology, Inc.: Vir is advancing tobevibart (VIR-3434) in a Phase 2 combination study as a potential treatment for patients with hepatitis B virus infection and in a Phase 2 combination study as a potential treatment for patients with hepatitis Delta virus infection;

Gilead Sciences, Inc.: Gilead is advancing teropavimab and zinlirvimab, two broadly neutralizing antibodies, in combination with lenacapavir, as a long-acting treatment for virologically suppressed people living with HIV;

Omeros Corporation: Omeros is advancing multiple Phase 2 studies evaluating OMS906 for the treatment of patients with PNH and other alternative pathway disorders; and

The company's partners are conducting preclinical studies of additional drug candidates engineered with these XmAb Fc domains.

Other Clinical Stage Drug Candidates

Obexelimab targets CD19 with its variable domain and uses the company's XmAb Immune Inhibitor Fc Domain, which is designed to inhibit the function of B cells, an important component of the immune system. In November 2021, the company licensed this drug candidate to Zenas BioPharma, which is conducting a Phase 3 study in patients with immunoglobulin G4-related disease (IgG4-RD) and a Phase 2 study in patients with warm autoimmune hemolytic anemia (wAIHA).

AIMab7195 (XmAb7195) uses the company's XmAb Immune Inhibitor Fc Domain and is designed to reduce blood levels of IgE, which mediates allergic responses and allergic disease. In February 2020, the company licensed this drug candidate to Aimmune Therapeutics, Inc., now a wholly owned subsidiary of Nestle S.A., which is evaluating the candidate in clinical studies for allergic indications.

Xpro1595 is a proprietary TNF inhibitor candidate which the company licensed to INmune Bio, Inc., in October 2017. INmune is advancing Xpro1595 through clinical development for patients with Alzheimer's disease and treatment-resistant depression.

Collaborations, Partnerships and Licensing Arrangements

A key part of the company's business strategy is to leverage the company's protein engineering capabilities, XmAb technologies, and XmAb drug candidates with partnerships, collaborations, and licenses.

Examples of arrangements the company has entered with the company's partners include:

Product Licenses: Johnson & Johnson, Genentech, Incyte Corporation, Nestle S.A., Zenas BioPharma, Inc., INmune Bio, Inc.

Novel Bispecific Antibody Collaborations: Johnson & Johnson, Astellas Pharma Inc., Amgen Inc., Novartis AG

Technology Licensing Agreements: Alexion Pharmaceuticals, Inc., Vir Biotechnology, Inc., Gilead Sciences, Inc., Omeros Corporation, Astria Therapeutics, Inc.

Strategic Collaborations: Caris Life Sciences

Product Licenses

Janssen Biotech, Inc., a Johnson & Johnson company

In October 2021, the company entered into an agreement with Janssen Biotech, Inc., a Johnson & Johnson company, to develop, manufacture, and commercialize plamotamab and to conduct research and development activities to discover novel CD28 bispecific antibodies against undisclosed B cell tumor targets. J&J will receive exclusive worldwide rights, subject to certain of the company's opt-in rights, to develop, manufacture and commercialize pharmaceutical products that contain one or more of such CD28 bispecific antibodies.

Pursuant to the agreement, the company is collaborating with J&J on further clinical development of plamotamab. With respect to the CD28 bispecific antibody collaboration, the company is generally responsible for conducting research activities, and J&J is generally responsible for all development, manufacturing, and commercialization activities for CD28 bispecific antibodies that are advanced.

In the first quarter of 2023, J&J selected a CD28 candidate that the company developed under the collaboration for further development. In the third quarter of 2023, J&J exercised its option on two additional CD28 candidates that were developed under the agreement. In the fourth quarter of 2023, J&J initiated a Phase 1 study with a CD28 candidate that was developed under the agreement.

Genentech

In February 2019, the company entered into an agreement with Genentech (Genentech, Inc. and F. Hoffman-La Roche Ltd) to develop and commercialize novel IL-15 cytokine therapeutics that use the company's bispecific Fc technology, including efbalropendekin alfa (XmAb306), declared as a Collaboration Product under the agreement.

Incyte Corporation

In July 2020, the FDA approved Monjuvi (tafasitamab-cxix) in combination with lenalidomide for treating certain patients with DLBCL, and the European Commission granted conditional marketing authorization to tafasitamab for treating certain patients with DLBCL, which is marketed as Minjuvi in Europe, in August 2021. In 2010, the company licensed exclusive worldwide rights to develop and commercialize tafasitamab (formerly MOR208 and XmAb5574) to MorphoSys AG. In February 2024, Incyte acquired exclusive global development and commercialization rights to tafasitamab. Tafasitamab, which the company engineered with an XmAb Cytotoxic Fc Domain, is the second XmAb medicine to be approved by the FDA.

Tafasitamab is marketed by Incyte under the brand name Monjuvi in the U.S. and is marketed under the brand name Minjuvi in Europe and Canada.

Nestle S.A./Aimmune Therapeutics, Inc.

In February 2020, the company granted Aimmune Therapeutics, Inc., an exclusive worldwide license to develop and commercialize XmAb7195, which was renamed AIMab7195. Aimmune was subsequently acquired by Nestle S.A. Nestle is responsible for all further development of AIMab7195.

INmune Bio, Inc.

In October 2017, the company entered into an agreement with INmune Bio, Inc., for an exclusive license to the company's Xpro1595 drug candidate. In connection with the license, the company received shares of INmune common stock.

The company is also eligible to receive a percentage of sublicensing revenue received for Xpro1595 and royalties in the mid-single digit percentage range on the sale of approved products. INmune is conducting Phase 2 studies in early Alzheimer's disease and treatment resistant depression.

Zenas BioPharma, Inc.

In November 2020, the company entered into an agreement with Zenas BioPharma (Cayman) Limited, now Zenas BioPharma, Inc., (Zenas) to which the company licensed the exclusive worldwide rights to develop and commercialize three preclinical-stage Fc-engineered drug candidates for autoimmune disease: XmAb6755 (ZB002), XPro9523 (ZB004), and XmAb10171 (ZB003). These programs incorporate an Xtend Fc Domain, a Cytotoxic Fc Domain, or both.

In November 2021, the company entered into a second agreement with Zenas to which the company licensed the exclusive worldwide rights to develop and commercialize obexelimab, a bifunctional antibody that targets CD19 with its variable domain and uses the company's XmAb Immune Inhibitor Fc Domain. In 2023, Zenas initiated a Phase 3 study in patients with immunoglobulin G4-related disease (IgG4-RD) and a Phase 2 study in patients with warm autoimmune hemolytic anemia (wAIHA).

Novel Bispecific Antibody Collaborations

Janssen Biotech, Inc., a Johnson & Johnson company

In November 2020, the company entered into an agreement, with J&J to develop XmAb bispecific antibodies against CD28 and a prostate tumor target, for the potential treatment of patients with prostate cancer. Under the agreement, the company conducted research activities to develop CD28 bispecific drug candidates for further development by J&J.

Astellas Pharma Inc.

In March 2019, the company entered into an agreement with Astellas Pharma Inc., under which the company applied its XmAb bispecific Fc technology to an antigen pair provided by Astellas and generated bispecific antibody candidates for further certain characterization and testing. Astellas was granted a worldwide exclusive license, with the right to sublicense products in the field created by the research activities.

Astellas selected ASP2138, a CLDN18.2 x CD3 XmAb 2+1 bispecific antibody developed under the collaboration, for further development and is conducting a Phase 1 study of ASP2138 in patients with gastric, gastroesophageal, and pancreatic cancers.

Amgen Inc.

In September 2015, the company entered into an agreement with Amgen Inc. to develop and commercialize bispecific antibody product candidates using the company's proprietary XmAb bispecific Fc technology.

Amgen applied the company's XmAb bispecific Fc technology to create xaluritamig (AMG 509), a STEAP1 x CD3 XmAb 2+1 bispecific antibody.

Amgen is completing enrollment in a Phase 1 study of xaluritamig in patients with mCRPC. In October 2023 at the European Society for Medical Oncology (ESMO) Congress, encouraging interim clinical results from the study were presented during an oral proffered paper session, which validates the potential of the XmAb 2+1 format. Amgen is planning two additional Phase 1 studies of xaluritamig to evaluate preliminary efficacy and safety in patients with early prostate cancer.

Novartis AG

In connection with the company's June 2016 agreement with Novartis, the company applied its XmAb bispecific Fc technology to a target pair antibody selected by Novartis. Novartis is responsible for development and commercialization of the program. Novartis is evaluating an undisclosed XmAb bispecific antibody candidate.

Technology Licensing Agreements

The company enters into technology licensing agreements in which the company licenses access to one or more of the company's XmAb Fc technologies on a restricted basis, typically to the company's XmAb Cytotoxic Fc Domain and/or its Xtend Fc Domain. The company's partners are responsible for all research, development and commercialization activities of the drug candidates. The plug-and-play nature of XmAb Fc domains allows the company to license access to its platforms with no internal research and development activities required of the company.

Alexion Pharmaceuticals, Inc.

Ultomiris (ravulizumab-cwvz) was the first antibody incorporating XmAb Fc technology to be approved by the FDA for commercial marketing. It is approved in the U.S. and multiple global markets for the treatment of certain patients with paroxysmal nocturnal hemoglobinuria (PNH), certain patients with atypical hemolytic uremic syndrome (aHUS) and certain patients with generalized myasthenia gravis (gMG). It is approved in the EU and Japan for the treatment of certain adult patients with neuromyelitis optica spectrum disorder (NMOSD). Ultomiris is commercialized by Alexion Pharmaceuticals, Inc.

In 2013, the company licensed Alexion the right to access its Xtend Fc domain, which Alexion used to develop an improved version of Alexion's commercialized Soliris product. The Xtend technology increased the circulating half-life of Ultomiris by over three-fold compared to Soliris and extended the dosing schedule to bimonthly for Ultomiris compared to biweekly for Soliris.

Vir Biotechnology, Inc.

In March 2020, the company entered into an agreement in which the company provided Vir a non-exclusive license to the company's Xtend technology to extend the half-life of novel antibodies, including sotrovimab, that Vir has investigated as potential treatments for patients with COVID-19. Vir, along with alliance partner GSK, is responsible for all research, development, regulatory and commercial activities for COVID-19 antibodies.

In August 2019, the company entered into an agreement with Vir Biotechnology, Inc., in which the company provided Vir a non-exclusive license to the company's Xtend technology for two targets in infectious disease. Tobevibart (VIR-3434) is being evaluated in a Phase 2 combination study as a potential treatment for patients with hepatitis B virus infection and in a Phase 2 combination study as a potential treatment for patients with hepatitis Delta virus infection.

Gilead Sciences, Inc.

In January 2020, the company entered into an agreement with Gilead Sciences, Inc., in which the company provided Gilead an exclusive license to the company's Cytotoxic Fc and Xtend Fc technologies for broadly neutralizing anti-HIV antibodies. Gilead is responsible for all development and commercialization activities. In 2023, Gilead initiated a Phase 2 study including two antibody candidates developed with the company's Fc technologies, teropavimab and zinlirvimab.

Omeros Corporation

In August 2020, the company entered into an agreement with Omeros Corporation, in which the company provided Omeros a non-exclusive license to its Xtend Fc technology, an exclusive license to apply the company's Xtend Fc technology to an initial identified antibody, OMS906, and options to apply the company's Xtend Fc technology to three additional antibodies. Omeros is responsible for all development and commercialization activities. In 2023, Omeros initiated a Phase 2 study of OMS906, a MASP-3 targeted antibody, in patients with PNH.

Astria Therapeutics, Inc.

In May 2018, the company entered into an agreement with Astria Therapeutics, Inc (formerly Quellis Biosciences, Inc.), in which the company provided Astria a non-exclusive license to the company's Xtend Fc technology to apply to an identified antibody. Astria is responsible for all development and commercialization activities.

Strategic Collaborations

The company enters into strategic collaborations where the company can create synergies between its partners' capabilities and assets and the company's own protein engineering capabilities, Fc technologies and XmAb drug candidates. Through these arrangements, the company seeks to create new drug candidates, investigate novel combination therapies and potentially identify additional indications for the company's portfolio of XmAb drug candidates.

Caris Life Sciences

In July 2022, the company entered into a research discovery agreement with Caris Life Sciences (Caris). The company received exclusive options to research, develop and commercialize products directed up to three targets. In December 2022, the company expanded its Caris collaboration with a second agreement.

Technology License Agreement and Service Agreement with Gale Therapeutics Inc.

In the fourth quarter of 2023, the company formed a subsidiary, Gale Therapeutics Inc. (Gale), to develop novel drug candidates that incorporate the company's XmAb technologies. In December 2023, the company entered into a Technology License Agreement (Gale License Agreement) with Gale, in which Gale received an exclusive worldwide, royalty-bearing, non-transferable license to preclinical assets in exchange for royalties on future sales and an option on future drug candidates that Gale will develop. Concurrently, the company entered into a Services Agreement (Gale Services Agreement) to provide research and development services and administrative support to Gale.

Intellectual Property

The company's patent estate, on a worldwide basis, includes over 1,500 issued patents and pending patent applications, which the company owns, with claims directed to XmAb Fc domains, all of the company's clinical and preclinical stage product candidates and the company's computational protein design methods and platforms. The company also has a large number of issued patents and pending patent applications with claims directed specifically to the company's XmAb technology and candidates.

The company has obtained registrations for the Xencor trademark, as well as certain other trademarks, which the company uses in connection with its pharmaceutical research and development services and the company's clinical-stage products, including XmAb. The company has registrations for Xencor and XmAb in the United States, Australia, Canada, the European Union, the United Kingdom, and Japan; and for Proteins by Design in the United States, Australia, Canada, and the European Union and the United Kingdom.

Third Party Vendors and Suppliers

KBI Biopharma, Inc.

In July 2014, the company entered into a master services agreement (KBI Agreement) with KBI Biopharma, Inc. (KBI). The company has engaged KBI under the KBI Agreement for process development, clinical scale-up, analytical method development, formulation development, and other services related to drug substance and drug product for the company's bispecific antibody and cytokine development candidates: plamotamab, vudalimab, XmAb104, XmAb306, XmAb564 and XmAb541 in accordance with cGMP regulations.

Cell Line Agreements with Selexis

In December 2015, the company entered into a master service agreement (Selexis Agreement) with Selexis SA (Selexis) for the manufacture of Selexis cell lines. Under the terms of the Selexis Agreement, Selexis will manufacture cell lines for the antibody candidates provided by the company and upon completion of the cell lines, the company has the option to take an unrestricted commercial license to the cell line.

Selexis has manufactured cell lines for certain of the company's bispecific antibody and cytokine drug candidates, and the company has rights to obtain commercial licenses to the Selexis cell line for the following bispecific antibody and cytokine candidates: plamotamab, vudalimab, XmAb104, XmAb306, XmAb564, and XmAb819.

License Agreement with BIO-TECHNE Corporation (BIO-TECHNE)

In April 2021, the company entered into an agreement with BIO-TECHNE for a non-exclusive license to a certain recombinant monoclonal antibody reactive with human Claudin-6 (CLDN6). The company is using this protein in its XmAb541 drug candidate.

Umbrella Development Services Agreement with Patheon Biologics LLC

In September 2018, the company entered into an Umbrella Development Services Agreement (Patheon Agreement) with Patheon Biologics LLC (Patheon). Under the terms of the Patheon Agreement, any of the affiliates within the global network of service sites in Thermo Fisher Scientific Inc.'s Pharma Services Group may perform clinical manufacturing and development services for the company in accordance with cGMP regulations.

Patheon is manufacturing drug substance material for the company's XmAb819 program and drug product for the company's plamotamab program.

Master Services Agreement with WuXi Biologics (Hong Kong) Limited

In February 2021, the company entered into a Master Services Agreement (WuXi Agreement) with WuXi Biologics (Hong Kong) Limited (WuXi). Under the terms of the WuXi Agreement, WuXi and its affiliates will perform manufacturing, analytical, development and other services for Xencor in accordance with applicable regulations. The WuXi Agreement includes customary rights to replacement of non-conforming products.

WuXi is manufacturing drug substance and drug product for the company's XmAb808 and XmAb662 programs.

Master Clinical Services Agreement with ICON Clinical Research Limited

In April 2016, the company entered into a Master Clinical Services Agreement (ICON Agreement) with ICON Clinical Research Limited (ICON), which was amended in April 2021. Under the terms of the ICON Agreement, ICON and its affiliates will perform clinical trial services (including site selection, study design, site monitoring, management and training, and patient selection) for Xencor in accordance with applicable regulations.

ICON is providing services to the company in connection with ongoing Xencor-sponsored clinical trial that target oncology indications.

Master Services Agreement with Innovaderm Research, Inc.

In April 2022, the company entered into a Master Services Agreement (Innovadrem Agreement) with Innovaderm Research, Inc. (Innovaderm). Under the terms of the Innovaderm Agreement, Innovaderm will perform clinical trial management and clinical development services (including site selection, study design, site monitoring, management and training, and patient selection) for Xencor in accordance with applicable regulations.

Innovaderm is conducting clinical studies for the company's XmAb564 program.

Master Services Agreement with PPD Development, L.P.

In June 2015, the company entered into a Master Services Agreement (PPD Agreement) with PPD Development, L.P. (PPD). Under the terms of the PPD Agreement, PPD will perform clinical trial management and clinical development services (including site selection, study design, site monitoring, management and training, and patient selection) for Xencor in accordance with applicable regulations.

PPD is conducting clinical studies for the company's vudalimab program.

Master Services Agreement with Vetter Pharma International GmbH

In October 2020, the company entered into a master services agreement (Vetter Agreement) with Vetter Pharma International GmbH (Vetter). The company has engaged Vetter under the Vetter Agreement for clinical scale-up, analytical method development, formulation development, and other services related to manufacturing drug product for the company's bispecific antibody candidates vudalimab and XmAb541 in accordance with cGMP regulations. For each bispecific program, the company has entered into a separate agreement with the terms and conditions of services and payment. The Vetter Agreement is for an eight-year term but is automatically extended on an annual basis until the services are completed.

Vetter is manufacturing drug product for the company's vudalimab and XmAb541 programs.

Master Services Agreement with OncoBay Clinical, Inc.

In August 2023, the company entered into a Master Services Agreement (OncoBay Agreement) with OncoBay Clinical, Inc. (OncoBay). Under the terms of the OncoBay Agreement, OncoBay will perform Contract Research Organization (CRO) services, including clinical trial management and clinical development services (including site selection, study design, site monitoring, management and training, and patient selection) for Xencor in accordance with applicable regulations.

OncoBay is conducting clinical studies for the company's XmAb541 program.

Regulatory Overview

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing, and distribution of drugs and biologics. These agencies and other federal, state and local entities regulate research and development activities and the testing, manufacture, quality control, safety, effectiveness, labeling, storage, recordkeeping, approval, advertising and promotion, and export and import of the company's product candidates.

The company's product candidates are subject to regulation by the FDA as a biologic.

Any biologic products for which the company or its collaborators receive FDA approvals are subject to continuing regulation by the FDA, including among other things, cGMP compliance for product manufacture, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, complying with certain electronic records and signature requirements, and complying with FDA promotion and advertising requirements, which include, among others, restrictions on direct-to-consumer advertising, promoting biologics for uses or in patient populations that are not described in the product's approved labeling (known as 'off-label use'), industry-sponsored scientific and educational activities, and promotional activities involving the internet.

History

Xencor, Inc. was founded in 1997. The company was incorporated in California in 1997 and reincorporated in Delaware in 2004.