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Atacicept demonstrated stabilization of eGFR through 72 weeks in the ORIGIN Phase 2b trial in IgAN

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Atacicept

  • Novel biologic investigational therapeutic: recombinant fusion protein containing the soluble TACI receptor that binds to the cytokines BAFF 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
  • Low nanomolar potency vs BAFF (Kd 1.45 nM) and APRIL (Kd 0.672 nM);3 t1/2 = 35 days4
  • Atacicept has been studied in clinical trials including >1,500 patients across multiple indications5 and has a generally well-tolerated safety profile in IgAN6,7
  • At home self-administration by once weekly 1-mL subcutaneous injection
  • Vera holds exclusive worldwide rights for the development and commercialization of atacicept in all indications

BAFF = B-cell activating factor; APRIL = A proliferation-inducing ligand; ; TACI = transmembrane activator and calcium-modulator and cyclophilin ligand interactor.

1Cheung CK, et al. Front Nephrol 2023; 2Dillon SR, et al. Arthritis Res Ther 2010; 3Vera data on file; 4Willen D, et al. Eur J Drug Metab Pharmacokinet 2020; 5Gordon C, et al. Rheumatol Adv Pract 2019 and data on file; 6Lafayette R, et al. Kidney Int 2024; 7Lafayette R, et al. ERA 2024, abstr 812.

IgA Nephropathy (IgAN)

IgAN, also known as Berger’s disease, is a B-cell mediated kidney disease driven by the deposition of abnormal immune complexes that accumulate in the kidneys, causing inflammatory tissue damage and kidney failure1

IgAN is a serious, immune-mediated, progressive disease with an average age at diagnosis of ~35 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

Despite current standard of care with ACEi/ARBs and CKD supportive care,5 kidney function may steadily decline6

There is a high unmet medical need for safe and effective new disease-modifying treatments for IgAN that target the upstream source of disease7

ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; CKD = chronic kidney disease.
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; 6Cheung CK, et al. J Clin Med 2021; 7Huang X, Xu G. Front Pharmacol 2021.

BAFF & APRIL Dual Inhibition for IgAN

Atacicept: Dual Inhibitor of BAFF and APRIL

Rational Drug Design: Native TACI Receptor Fused to Fc — Fully Humanized Soluble Fusion Protein
1
BAFF and APRIL are upregulated and stimulate B cells through the TACI receptor, causing increased Gd-IgA1 production…
2
…autoantibodies bind to exposed Gd-IgA1 hinge region…
3
…and form immune complexes…
4
…which deposit in the mesangium, resulting in glomerular inflammation (nephritis)…
5
…and progressive kidney injury with hematuria, proteinuria, and eGFR decline
1
BAFF and APRIL are upregulated and stimulate B cells through the TACI receptor, causing increased Gd-IgA1 production…
2
…autoantibodies bind to exposed Gd-IgA1 hinge region…
3
…and form immune complexes…
4
…which deposit in the mesangium, resulting in glomerular inflammation (nephritis)…
5
…and progressive kidney injury with hematuria, proteinuria, and eGFR decline
Cheung CK, et al. Front Nephrol 2024.
1
By inhibiting BAFF and APRIL, atacicept decreases B cell production of Gd-IgA11
2
…leading to a reduction in autoantibodies2 binding to Gd-IgA1…
3
…and fewer immune complexes3
4
This may lead to less glomerular deposition and reduced glomerular inflammation (nephritis)…
5
…which may result in hematuria reduction,4 proteinuria reduction,5 and eGFR stabilization5
1
By inhibiting BAFF and APRIL, atacicept decreases B cell production of Gd-IgA11
2
…leading to a reduction in autoantibodies2 binding to Gd-IgA1…
3
…and fewer immune complexes3
4
This may lead to less glomerular deposition and reduced glomerular inflammation (nephritis)…
5
…which may result in hematuria reduction,4 proteinuria reduction,5 and eGFR stabilization5
Fc = fragment crystallizable region; IgG1 = immunoglobulin G1.
1Lafayette R, et al. Kidney Int 2024; 2Barratt J, et al. Nephrol Dial Transplant 2022;3 suppl 3, abstr FC051; 3Barratt J, et al. ASN Kidney Week 2022, abstr SA-PO655; 4Floege J, et al. ERA 2024, abstr 123; 5Lafayette R, et al. ERA 2024, abstr 812.

Phase 2b Clinical Data

Origin

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

Randomized Treatment Period Results: Atacicept vs Placebo1,2

  • Atacicept met the primary endpoint at 24 weeks
  • At 36 weeks, atacicept showed statistically significant Gd-IgA1 reduction, hematuria resolution, UPCR reduction, and eGFR stabilization compared with placebo
  • Atacicept safety profile was well tolerated, similar to placebo

Atacicept 72-week Data is Consistent With Disease Modification in IgAN3

Reduction in Gd-IgA1

Reduction in Hematuria

Reduction in Proteinuria

Stabilization of eGFR

1Lafayette R, et al. Kidney Int 2024; 2Floege J, et al. ERA 2024, abstr 123; 3Lafayette R, et al. ERA 2024, abstr 812; 4Mean ± SE; 5Change from baseline in number of participants with hematuria at each visit divided by number with baseline hematuria. 72-week atacicept data includes participants originally randomized to any atacicept dose (25 mg, 75 mg, 150 mg) during the double-blind period in the intent-to-treat population for Gd-IgA1, hematuria, and eGFR, and week 36 per-protocol population for UPCR.

Participants who switched from placebo to atacicept showed similar results to 36-week outcomes in participants originally randomized to atacicept

  • Atacicept safety: well tolerated, consistent with randomized period
  • 91% retention rate at 72 weeks

Learn More

For more information, contact MEDINFO@VERATX.COM

BAFF is also known as B Lymphocyte Stimulator or BLyS.

Watch this video to learn about atacicept’s mechanism of action in IgAN and 36-week results from the ORIGIN Phase 2b clinical trial of atacicept in IgAN

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, or contact clinicaltrials@veratx.com

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