11 February 2019 - - US-based immunotherapy company Alpine Immune Sciences, Inc. (NASDAQ: ALPN) has initiated dosing in its first-in-human Phase I study of ALPN-101, a first-in-class dual ICOS/CD28 antagonist, the company said.

This study will evaluate the safety and tolerability of single- and multiple-ascending intravenous and/or subcutaneous doses of ALPN-101.

In addition, pharmacokinetics, pharmacodynamics, and exploratory biomarkers are being evaluated to help determine ALPN-101's potential for the treatment of autoimmune and inflammatory diseases.

The company expects data later in 2019.

AIS-A01 is a randomised, placebo-controlled, blinded study in adult healthy volunteers to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of ALPN-101.

The trial is being conducted in Australia.

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 simultaneously inhibiting the CD28 and ICOS inflammation pathways.

CD28 and ICOS are closely related costimulatory molecules with partially overlapping roles in T cell activation likely connected to multiple autoimmune and inflammatory diseases.

In preclinical models of graft versus host disease, inflammatory arthritis, and multiple sclerosis, ALPN-101 demonstrates efficacy superior to blockade of the CD28 or ICOS pathways alone.

ALPN-101 was engineered using Alpine's vIgD platform, which uses directed evolution to transform native IgSF proteins into multifunctional protein therapeutics.

Alpine Immune Sciences, Inc. is committed to leading a new wave of functional immune therapeutics. Alpine is employing directed evolution to create potentially powerful multifunctional immunotherapies to improve patients' lives. Alpine has two lead programs.

The first, ALPN-101 for autoimmune/inflammatory diseases, is a dual ICOS/CD28 antagonist, engineered to reduce pathogenic immune responses.

The second, ALPN-202 for cancer, is a dual PD-L1/CTLA-4 antagonist and PD-L1-dependent CD28 costimulator intended to combine checkpoint inhibition with T cell costimulation an approach currently absent from approved checkpoint therapies.