ALPN-303

Dual BAFF/APRIL B cell cytokine antagonist with best-in-class potential

ALPN-303 is a dual B cell cytokine antagonist being developed for multiple autoimmune and inflammatory diseases.

ALPN-303 is a dual B cell cytokine antagonist being developed for multiple autoimmune and/or inflammatory diseases. Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, ALPN-303 in preclinical studies shows robust inhibition of B cell activating factor/B lymphocyte stimulator (BAFF, BLyS) and a proliferation inducing ligand (APRIL). These two pleiotropic B cell cytokines play key roles in B cell development, differentiation, and survival, and together contribute to the pathogenesis of multiple autoimmune diseases like systemic lupus erythematosus (SLE) and many other autoantibody-related inflammatory diseases. By simultaneously blocking these two cytokines, ALPN-303 has the potential to improve outcomes in patients suffering from severe autoimmune and/or inflammatory diseases.

Data from RUBY-1, a Phase 1 study of ALPN-303 in healthy volunteers, and a summary of our nonclinical studies, were presented at our inaugural R&D Day in September 2022, demonstrating that:

  • ALPN-303 has significantly improved potency against BAFF, and particularly APRIL, and demonstrates superiority against BAFF- or APRIL-only inhibitors, as well as wild-type TACI, in preclinical disease models.
  • ALPN-303 was well tolerated in healthy adults when administered intravenously or subcutaneously (SQ) at doses up to 960 mg.
  • Encouraging preliminary pharmacodynamic analyses, including reductions in circulating immunoglobulins and antibody-secreting cells (CD38hi plasmablasts/plasma cells) – the latter not previously reported with inhibitors of BAFF and/or APRIL in healthy adults, to the best of the Company’s knowledge.
  • Pharmacodynamic analyses further support the feasibility of convenient subcutaneous therapeutic dosing every four weeks, suggesting potential for more robust activity and greater convenience over related inhibitors of BAFF and/or APRIL.
  • Doses selected for patient-based studies include 80 mg and 240 mg SQ every four weeks.

We believe the encouraging data from the RUBY-1 study support a broad development plan including:

  • A randomized, placebo-controlled phase 2 proof-of-concept study in SLE; and
  • Open-label basket studies in renal, hematologic, and dermatologic autoimmune diseases with initial data anticipated in the second half of 2023.

For more information on our ongoing clinical trials please refer to the clinical trials portion of our website.

For additional information please refer to our corporate filingscorporate presentation, scientific publications, and our September 2022 R&D Day presentation.

ALPN-303: Engineered inhibitor of BAFF (BLyS) and APRIL, clinically-validated cytokine pathway that plays key roles in B cell development, differentiation, and survival, and together contribute to the pathogenesis of multiple autoimmune diseases like lupus and many other autoantibody-related inflammatory diseases.

ALPN-303 Addresses a Key Weakness in WT TACI
ALPN-303 improves affinity of TACI against BAFF 8 to 10-fold, and dramatically improved the affinity against APRIL.

ALPN-303 Reduces Antibody-Secreting Cells*

TrialIndication(s)DesignNData TimingEnables
Ruby 2Systemic Lupus ErythematosusPhase 2 Randomized Proof-of-concept1922026Phase 3 / Pivotal
Ruby 3IgA Nephropathy Lupus Nephritis 1° Membranous NephropathyPhase 1b Open-Label Basket18-362H23Reg / Accel
Ruby 4Immune Thrombocytopenia Warm Autoimmune Hemolytic Anemia Cold Agglutinin DiseasePhase 1b Open-Label Basket21-422H23Reg / Accel
Ruby 5Pemphigus Vulgaris or Foliaceous Bullous PemphigoldPhase 1b Open-Label Basket12-241H24Reg / Accel

SLE Phase 2 anticipated to enable pivotal phase 3 development.
Basket studies anticipated to enable accelerated development in multiple indications.

Join us in the discovery and development of next-generation immunotherapies.

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