Company: VERA
Filing Date: 2025-02-28
Form Type: 10-K
Source: 0000950170-25-029969
Chunk: 190

Company: Vera Therapeutics, Inc.
Filing Date: 2025-02-28
Form: 10-K
Item: Item 1
Chunk 190
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 Our Proposed Solution

There are approximately 50,000 patients in the United States with pMN. In 70-80% of cases, inflammation of the renal glomeruli is caused by autoantibodies targeting the proteins phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). The remaining 20-30% of cases develop as a secondary condition due to underlying issues such as infections, other autoimmune diseases, tumors, or drug poisoning. Most patients with biopsy-confirmed primary membranous nephropathy (pMN) have circulating anti-PLA2R autoantibodies, with approximately 70% of pMN cases associated with anti-PLA2R+ antibodies, and 65% of these cases considered moderate-to-severe. According to current KDIGO guidelines, PLA2R is recognized as a crucial diagnostic marker, eliminating the need for a kidney biopsy if the patient is seropositive for PLA2R and exhibits clinical symptoms. Additionally, the concentration of anti-PLA2R antibodies provides insights into disease activity and progression, serving as a clinical criterion for assessing the risk of progressive renal failure in pMN patients: 1) higher antibody concentrations indicate more active pMN and a greater risk of kidney failure, and 2) monitoring antibody levels can predict phases of clinical remission and relapses, as changes in anti-PLA2R antibody levels typically precede improvements or worsening of the disease.

Current treatments tackle the autoimmune aspect of pMN through B-cell depletion (e.g., agents such as rituximab) or immunosuppression via cyclophosphamide / high dose steroids; these therapies have been associated with significant toxicity. With no FDA-approved pMN therapies, significant unmet need remains for efficacious and safe agents, including those that can reduce adverse events associated with immunosuppressant therapy, offer benefit for the ~40% of patients that are refractory to rituximab, and further reduce disease progression to CKD and ESRD.

A more targeted approach that focuses on modulating autoimmune B-cell production, rather than broad immunosuppression, may offer a potential solution. Autoreactive B-cells are implicated in the immunopathogenesis of primary membranous nephropathy (pMN), with the phospholipase A2 receptor (PLA2R) identified as the target antigen for the typical immunoglobulin G (Ig