Vera Therapeutics

Our Science

Atacicept

  • Novel biologic investigational therapeutic: recombinant fusion protein containing the soluble TACI receptor that binds to the cytokines BLyS and APRIL, members of the tumor necrosis factor family that stimulate B cells and plasma cells to produce autoantibodies associated with IgA nephropathy (IgAN)1 and lupus nephritis (LN)2
  • Well-tolerated safety profile in clinical studies including >1,500 patients across multiple indications3
  • Self-administered once weekly by 1-mL subcutaneous injection
  • Vera holds an exclusive worldwide license for the development and commercialization of atacicept in all indications from Merck KGaA, Darmstadt, Germany, a leading science and technology company

BLyS = B lymphocyte stimulator, also known as B-cell activating factor or BAFF; APRIL = A proliferation-inducing ligand; TACI = transmembrane activator and CAML interactor.

1Macpherson AJ, et al. Mucosal Immunol 2008; 2Dillon SR, et al. Arthritis Res Ther 2010; 3Gordon C, et al. Rheumatol Adv Pract 2019 and data on file.

IgA Nephropathy (IgAN)

IgAN, also known as Berger’s disease, is an autoimmune disease driven by the deposition of abnormal immune complexes that accumulate in the kidneys, causing inflammatory tissue damage and kidney failure

IgAN is a serious and progressive disease with an average age at diagnosis of 30 years old, leading to severe impact on quality of life2
Up to 50% of IgAN patients progress to end-stage kidney disease within 20 years, requiring dialysis or kidney transplant3,4
Current standard of care includes ACE inhibitors and ARBs to manage blood pressure5
There is a high unmet medical need for safe and effective new treatments for IgAN that target the upstream source of disease6,7

ACE = angiotensin-converting enzyme; ARB = angiotensin II receptor blocker.
1Wyatt RJ, et al. N Engl J Med 2013; 2Jarrick S, et al. J Am Soc Nephrol 2019; 3Kwon CS, et al. J Health Econ Outcomes Res 2021; 4Pitcher D, et al. Clin J Am Soc Nephrol 2023; 5KDIGO 2021; 6Maixnerova D, et al. J Clin Med 2022; 7Huang X, Xu G. Front Pharmacol 2021.

BLyS/APRIL Dual Inhibition

Click below to learn why dual inhibition of BLyS/APRIL matters

  • BLyS and APRIL stimulate B cells and plasma cells to produce disease-causing antibodies associated with autoimmune disease1
  • Both cytokines are elevated in patients with IgAN and are each associated with clinical severity2-4
  • In preclinical models, overexpression of BLyS alone can lead to the development of kidney IgA deposits and IgA-like nephritis5
  • BLyS can directly increase the expression of factors associated with fibrosis and inflammation in mesangial cells3
  • BLyS or APRIL alone are each capable of independently supporting plasma cell survival6,7
  • Dual inhibition of BLyS and APRIL decreased renal damage in an immunologic animal model more than individual inhibition of either pathway alone6
  • Inhibiting both biologic targets may avoid compensatory increase in parallel signal8,9
  • Inhibiting APRIL alone may lead to upregulation of BLyS signaling with potential consequences on efficacy10

While BLyS is known to bind all three receptors, its biologic effect is lessened when binding mature B-cell TACI and BCMA.
1Schneider P. Curr Opin Immunol 2005; 2Xin G, et al. J Nephrol 2013; 3Cao Y, et al. Mol Med Rep 2020; 4Zhai Y, et al. Medicine (Baltimore) 2016; 5McCarthy D, et al. J Clin Invest 2011; 6Haselmayer P, et al. Eur J Immunol 2017; 7Benson M, et al. J Immunol 2008; 8Yeh T, et al. J Allergy Clin Immunol 2020; 9Tsiantoulas et al. Nature 2021; 10Vallerskog T, et al. Arthritis Res Ther 2006.

Target The Source

Atacicept is uniquely able to substantially reduce Gd-IgA1, the core of the immune complexes that cause disease progression and mortality in IgAN patients.1

Click through the pathway below to learn about the roles of BLyS, APRIL, and atacicept in IgAN pathophysiology

1

By blocking BLyS and APRIL, atacicept may reduce numbers of disease-causing B cells2-4
2

By blocking BLyS and APRIL, atacicept may reduce numbers of disease-causing plasma cells4-6
3

Reductions in plasma cells and antibody class switching to IgA reduce production of pathogenic Gd-IgA17-9
4

Reductions in B cells and plasma cells work together to lower production of autoantibodies to Gd-IgA110-12
5

Therefore, fewer immune complexes are formed13,14
6

This in turn reduces immune complex deposition in glomeruli and reduces complement activation10,11
7

Ultimately, progressive renal injury may be prevented

Gd-IgA1 = galactose-deficient immunoglobulin A1.
1Wyatt RJ, et al. N Engl J Med 2013; 2Xin G, et al. J Nephrol 2013; 3Cao Y, et al. Mol Med Rep 2020; 4Zhai Y-L, et al. Medicine (Baltimore) 2016; 5Benson MJ, et al. J Immunol 2008; 6Haselmayer P, et al. Eur J Immunol 2017; 7Bagchi S, et al. PLoS One 2019; 8Zheng S, et al. JCI Insight 2020; 9Lafayette R, et al. ERA 2023 late breaking oral presentation, June 17; 10Suzuki H, et al. J Clin Invest 2009; 11Xie X, et al. J Pathol 2021; 12Barratt J, et al. ERA 2022; 13Zhang X, et al. Clin J AM Soc Nephrol 2021; 14Barratt J, et al. ASN 2022.

View IGAN Publications

Phase 2b Clinical Data

Origin

Multinational, randomized, double-blind, placebo-controlled Phase 2b clinical trial evaluating the safety and efficacy of atacicept in patients with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression.

Results of the ORIGIN Double-Blind Treatment Period

Click each endpoint to learn more

Proteinuria

Met primary endpoint: statistically significant proteinuria reduction with atacicept vs placebo at 24 weeks

Atacicept 150 mg vs placebo in per-protocol analysis at 36 weeks: Δ43%; p = 0.003

eGFR
eGFR through 36 weeks
  • Placebo group showed expected decline
  • Atacicept 150mg led to stable eGFR
Difference in eGFR changes
  • Statistically significant: 11%; p=0.038
  • Clinically meaningful - 5.8 mL/min/1.73m2
Gd-IgA1

Δ64%, p<0.001

Gd-IgA1 reduction from baseline with atacicept 150 mg at 36 weeks

First B cell modulator to demonstrate substantial Gd-IgA1 reduction in a multinational, doubleblind placebo-controlled trial

Safety
Atacicept was well-tolerated through 36 weeks
  • No increased rate of infections compared to placebo
  • Low rate (2%) of serious adverse events overall
  • No drug discontinuations or interruptions due to hypogammaglobulinemia

View Full Presentation

Phase 3 Clinical Trial

Origin3

Multinational, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the safety and efficacy of atacicept 150 mg in adults with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression.

Currently recruiting—learn more at theORIGINiganstudy.com or clinicaltrials.gov

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