Vera Therapeutics (VERA) Study Result summary

Study background and rationale

• Atacicept is a dual-BAFF/APRIL inhibitor developed to target autoimmune diseases, with IgA nephropathy (IgAN) as the lead indication.

• IgAN is driven by abnormal B cell function, leading to immune complex formation and progressive kidney damage.

• The ORIGIN phase III trial aimed to demonstrate atacicept’s ability to reduce proteinuria and potentially prevent end-stage kidney disease.

• Atacicept’s mechanism is positioned as a targeted, less immunosuppressive alternative to steroids and B cell depletion.

• Atacicept is the first dual BAFF/APRIL inhibitor to show this magnitude of proteinuria reduction in a Phase 3 IgAN trial.

Study design and patient population

• ORIGIN phase III was a randomized, double-blind trial comparing atacicept 150 mg weekly to placebo in adults with IgAN; 431 participants were randomized 1:1 to self-administered subcutaneous injections.

• The primary endpoint was reduction in urine protein-to-creatinine ratio (UPCR) at week 36 in the first 203 participants.

• The full study enrolled 431 participants, with a secondary endpoint of eGFR change at 104 weeks; the trial continues in a blinded manner with results expected in 2027.

• Baseline characteristics included a mean age of ~40, significant proteinuria (~1.7 g/g), and ~65 mL/min eGFR, with over 50% on SGLT2 inhibitors.

• The population reflects a global, high-risk IgAN cohort with substantial loss of kidney function at enrollment.

Efficacy results

• At week 36, atacicept achieved a 46% reduction in UPCR from baseline and a 42% reduction versus placebo (p<0.0001).

• All other prespecified endpoints were consistent with or better than phase II-B results.

• The proteinuria reduction was robust across subgroups, with no single population driving the effect.

• The intention-to-treat analysis confirmed the magnitude and consistency of the effect.

• Long-term eGFR data from phase II-B showed stabilization of kidney function, supporting expectations for phase III outcomes.