Company: VERA
Filing Date: 2025-02-28
Form Type: 10-K
Source: 0000950170-25-029969
Chunk: 184

Company: Vera Therapeutics, Inc.
Filing Date: 2025-02-28
Form: 10-K
Item: Item 1
Chunk 184
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 domain of IgG1. TACI is a native receptor for BAFF and APRIL, members of the tumor necrosis factor family that promote B cell survival and autoantibody production associated with IgAN and other immunologic diseases. Dual blockade of BAFF and APRIL by TACI has been shown to be more potent than blocking BAFF alone or APRIL alone and has the benefit of targeting long-lived plasma cells, in addition to B cells, thus reducing production of Gd-IgA1 and its autoantibodies. Therefore, atacicept is designed to precisely modulate B cell activity by binding both BAFF and APRIL, and follows a long history of impactful agents that are logically designed Fc fusion proteins. This mechanism acts directly on the source of IgAN, which we believe will significantly mitigate the downstream effects of the disease.

Figure 4: Atacicept is the result of rational drug design

Atacicept’s specific actions on IgAN disease pathogenesis are shown in Figure 5 below.

Figure 5: Atacicept impact on IgAN pathogenesis

(1)Atacicept inhibits BAFF and APRIL, leading to decreased Gd-IgA1 production by B cells.

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(2)This leads to a reduction in the autoantibodies that bind to Gd-IgA1.

(3)Therefore, formation of pathogenic immune complexes is greatly reduced.

(4)This, in turn, reduces immune complex deposition in glomeruli and glomerular inflammation is reduced.

(5)Ultimately, progressive renal injury is attenuated, with reductions in hematuria and proteinuria, and stabilization of eGFR, which we believe will significantly lower the morbidity and mortality associated with IgAN.

Atacicept’s disease-modifying mechanism addresses the upstream processes that cause IgAN, while most other molecules in development act downstream. Therefore, we believe that the clinical outcomes of atacicept, measured by endpoints designed to assess efficacy and durability, will be favorable over competitors, with a demonstrated tolerability profile. Once weekly 1 mL subcutaneous dosing also provides an attractive target product profile for patients.

Atacicept in IgAN: clinical development

Atacicept was the subject of a collaboration agreement between Ares and ZymoGenetics, Inc. in 2001, and was licensed on an exclusive basis to Ares in 2008. It was advanced by Merck KG