Mechanism of Action

Telitacicept is a proprietary novel fusion protein of us to treat autoimmune diseases. It is constructed with the extracellular domain of the human transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor and the fragment crystallizable (Fc) domain of human immunoglobulin G (IgG). Telitacicept targets two cell-signaling molecules critical for B-lymphocyte development: B-cell lymphocyte stimulator (BLyS) and a proliferation inducing ligand (APRIL), which allows it to effectively reduce B-cell mediated autoimmune responses that are implicated in several autoimmune diseases.

BLyS (also known as B-cell activating factor, or BAFF) and APRIL are both involved in the development of B cells from pre-B lymphocytes to mature B cells, and ultimately to plasma cells, the professional cells producing antibodies, as well as in the co-stimulation of T-cell proliferation under certain conditions. Aberrant B cell activities and antibody production are known to be implicated in a number of autoimmune diseases. BLyS and APRIL function through the following mechanisms:

• BLyS binds to three types of membrane receptors expressed on B-cells, i.e., TACI, B-cell maturation antigen (BCMA) and B-cell activating factor receptor (BAFF-R), to inhibit cell death and stimulate differentiation of B cells into antibody-producing plasma cells. The interaction between BLyS and TACI induces a T-cell independent B-cell activation, immunoglobulin class-switching and B-cell homeostasis, while BLyS’ interaction with BCMA is important for the differentiation and survival of plasma cells.

• Unlike BLyS, APRIL only binds to TACI and BCMA (but not BAFF-R) to modulate the function and survival of B cells and promotes their differentiation into plasma cells.

• In sum, whereas BCMA binds to BLyS weakly and BAFF-R does not bind to APRIL, TACI binds to BLyS and APRIL with equal affinity and can also bind to heteromeric forms of BLyS and APRIL.

• BLyS and APRIL also play a role in the co-stimulation of T cells as B cells and T cells cross-talk. For instance, since BAFF-R is a potent T cell co-stimulator, the signalling of BLyS to BAFF-R could promote aberrant T cell maturation, which is known to be implicated in certain autoimmune diseases.

Consistent with their known functionalities, increased BLyS and APRIL expression has been observed in various B cell-mediated autoimmune diseases, such as SLE, NMOSD and RA. Studies have shown that direct inhibition of BLyS and APRIL has the potential to prevent the engagement of their receptors, BAFF-R, TACI and BCMA, and thus to prevent the subsequent activation of B cell-driven mechanisms, such as autoantibody production that contributes to the pathology of autoimmune diseases. BLyS and APRIL have therefore emerged as important targets for autoimmune therapeutics, although most of the clinical-stage drug candidates targeting this signaling pathway have been designed to neutralize either BLyS or APRIL, but not both.

As illustrated in the diagram below, Telitacicept blocks BLyS and APRIL from binding to BAFF-R, BCMA and TACI receptors expressed on B-cell surface, suppressing the BLyS and APRIL signaling, and inhibiting the development and survival of mature B cells and plasma cells.

Abbreviation: A3 = APRIL homotrimers; B3 = BLyS homotrimers; A2B = heterotrimers of two APRIL and one BLyS molecules; AB2 = heterotrimers of one APRIL and two BLyS molecules.


SLE is the lead indication of telitacicept. In SLE, we have completed a Phase IIb registrational study in China, where telitacicept showed a favorable efficacy and safety profile. We have completed registrational trials in SLE patients, and telitacicept has demonstrated potential strong clinical efficacy and best-in-class potential in treating SLE based on published data.

In addition to SLE, we are actively developing telitacicept for six other B cell-mediated autoimmune diseases in late-stage clinical trials in China, including two registrational studies in neuromyelitis optica spectrum disorder (NMOSD) and in rheumatoid arthritis (RA), two Phase II studies in indications with large patient populations but few efficacious treatments available, including IgA nephropathy (IgAN) and Sjögren’s syndrome (SS), and two additional Phase II studies in hard-to-treat rare diseases, including multiple sclerosis (MS) and myasthenia gravis (MG).

Competitive Advantages of Telitacicept

With its significant efficacy and favorable safety profile observed in SLE patients in the China trials, telitacicept has demonstrated the potential to become a global first-in-class and best-in-class biological therapy for SLE. We believe that telitacicept has the following major competitive advantages:

• Optimized structure design leads to improved biological activities and productivity.

• Full human amino acid sequence to minimize potential immunogenicity.

• Strong clinical efficacy profile.

• Favorable safety profile.


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