Alpine Immune Sciences Presents ALPN-101 Phase 1 Healthy Volunteer Study Data and Details of Upcoming Phase I/II BALANCE GVHD Study at the 61st American Society of Hematology Annual Meeting
ALPN-101 demonstrates ability to potently inhibit both T and B cell responses in first-in-human study
Human experience supports both IV and SQ dosing regimens
T cell costimulation via the CD28 and
ICOSpathways is critical to the pathogenesis of GVHD. Available therapies blocking the CD28 – CD80/86 pathway, such as abatacept and belatacept (CTLA4-Ig), may be at least partially beneficial in acute GVHD, but based on models they appear also to permit escape of ICOS+ T cells, which correlate with disease activity.
ALPN-101 is a dual inhibitor of CD28 and
ICOSand demonstrates potent efficacy in preclinical models. It exhibits a potent, unique activity superior to combinations of biologics individually antagonizing the CD28 – CD80/86 and ICOS– ICOSL pathways.
- In adult healthy volunteers, ALPN-101 has been well tolerated as single intravenous or subcutaneous doses, without cytokine release, infusion-related reactions, hypersensitivity, or other signs of agonist activity.
- Dose-dependent pharmacodynamic activity was observed, including inhibition of T cell activation, assessed ex vivo based on inhibition of staphylocococcal entereotoxin B (SEB)-induced cytokine production, and inhibition of antibody responses, assessed following immunization with keyhole limpet hemocyanin (KLH).
- Based on activity in models, together with favorable tolerability and pharmacodynamics in healthy volunteers, ALPN-101 has the potential to be a clinically meaningful immunomodulator for the treatment of inflammatory diseases such as GVHD.
- BALANCE is a Phase 1/2, first-in-disease dose escalation and expansion study of ALPN-101 in patients with active, steroid-refractory or steroid-resistant acute GVHD. It will explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ALPN-101.
“Despite decades of intense research, GVHD remains a major cause of morbidity and mortality after hematopoietic stem cell transplantation,” commented
About Graft Versus Host Disease (GVHD)
Graft versus host disease (GVHD) is the most common life-threatening complication of a hematopoietic cell transplant. It occurs when donor cells see recipient cells as foreign and attack them. Acute GVHD typically occurs within the early weeks and months after transplant, usually involving the skin, liver, and gastrointestinal tract. GVHD patients remain at risk of organ system damage and increased mortality due to the disease and to high dose glucocorticoids.
ALPN-101 is a novel Fc fusion protein of a human inducible T cell costimulator ligand (ICOSL) variant immunoglobulin domain (vIgD™), and a first-in-class therapeutic designed to inhibit simultaneously the CD28 and
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