Business Description

A. Overview We are a clinical-stage biopharmaceutical company focused on discovering and developing engineered antibody therapeutics to treat patients with cancer and autoimmune diseases, who have unmet medical needs. We use our protein engineering capabilities to design new technologies and XmAb ® drug candidates with improved properties and multi-target mechanisms of action. We advance these candidates into clinical-stage development, where we are conducting Phase 1 and Phase 2 studies for a broad portfolio of programs, to determine which programs to advance into later stages of development and potentially commercialization, which programs we partner to optimize development, and which programs we discontinue. Our 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 across antibodies, and our engineered Fc domains can be readily substituted for natural Fc domains. These Fc domains provide specific features such as bispecific structure and extended half-life and serve as the scaffolds for our XmAb drug candidates. We and our partners develop XmAb antibodies and other types of biotherapeutic drug candidates with improved properties and functionality, which can provide innovative approaches to potentially treating disease and clinical benefits over other treatment options. Applications of our protein engineering technologies include multi-specific antibodies that engage two or more targets simultaneously, creating entirely new biological mechanisms of anti-disease activity, or enhancement of antibody performance by increasing immune inhibitory activity, improving cytotoxicity, extending circulating half-life and stabilizing novel protein structures. Three marketed medicines have been developed with our XmAb protein engineering technologies. B. XmAb Bispecific Fc Domain and Multi-Specific Antibody Formats Our modular approach to protein engineering is a distinguishing feature of our Fc technologies. This flexibility enables us to design multiple XmAb drug candidates with distinct and novel mechanisms of action and to explore new applications of the XmAb Bispecific Fc Domain. Our business, research, and clinical efforts focus on developing and advancing a portfolio of XmAb drug candidates in oncology and autoimmune diseases. • CD3 bispecific antibodies : CD3 T-cell engaging bispecific antibodies are designed to redirect T cells to target cells by engaging an antigen on the target cell and CD3, an activating receptor on T cells. We have expanded the potential of our CD3 T-cell engagers through the development of the multi-specific XmAb 2+1 bispecific antibody format, which incorporates two identical target-binding domains and one CD3-binding domain. Target-binding affinities are engineered to enable selective engagement and killing of cells with high target expression while minimizing activity against normal cells with low target expression. In preclinical cancer models, XmAb 2+1 bispecific antibodies preferentially bound to tumor cells over normal cells and effectively recruited T cells to selectively kill tumor cells. These properties may be particularly important for solid tumor targets, where conventional monovalent targeting can result in limited tolerability due to target expression on normal tissues, including critical organs. XmAb819 and XmAb541 are examples of our CD3 candidates in clinical development for solid tumors that were designed using this 2+1 format. Plamotamab and XmAb657, which uses a 2+1 format, are examples of our CD3 candidates in clinical development for autoimmune diseases. • CD28 bispecific antibodies : T cells in the tumor microenvironment require both T-cell receptor engagement and co-stimulatory signaling to achieve full activation. CD28 is a key co-stimulatory receptor on T cells; however, its natural ligands are often not expressed on tumor cells. Targeted CD28 T-cell engaging bispecific antibodies may enable conditional co-stimulation of T cells, such as in the presence of tumor-associated antigens or in combination with CD3 T-cell engaging bispecific antibodies.…