Dosing starts in study of potential myasthenia gravis therapy S-1117
Phase 1 trial is recruiting up to 96 healthy adults to assess treatment's safety
Dosing has started in the first group of healthy adults participating in a clinical study of S-1117, a candidate treatment Seismic Therapeutic designed to break down harmful self-reactive antibodies in autoimmune diseases like myasthenia gravis (MG).
Running at a single site in Australia, the Phase 1 clinical study (NCT06828393) is recruiting up to 96 adults, ages 18-65, who are in good physical and mental health. Its main goal is to assess how safe S-1117 is against a placebo, which will be done by monitoring the participants for side effects over two months.
“The start of our first-in-human study of S‑1117 marks a significant milestone for Seismic as we transition to a clinical stage company,” Jo Viney, PhD, Seismic’s CEO, said in a company press release.
Seismic utilizes machine learning, a branch of artificial intelligence that empowers computers to learn from data and make predictions, through its IMPACT platform to develop new biologic medicines.
“S‑1117 validates our founding belief that we have the potential to create transformative medicines by leveraging machine learning through our IMPACT platform, guided by the best minds in immunology to discover novel biologics,” Viney said.
Going after the self-reactive antibodies
Like other autoimmune diseases, MG occurs when the immune system mistakes healthy tissue or its components as foreign and produces self-reactive antibodies that trigger inflammation and damage. In MG, antibodies target proteins involved in nerve-muscle communication, causing the disease’s hallmark symptoms of muscle weakness and fatigue.
S-1117 is an engineered enzyme that cleaves immunoglobulin G (IgG) antibodies, the most common type of antibody, including those that cause autoimmune diseases. By breaking them apart, S-1117 should promote the antibodies’ degradation and help lower their levels in the blood, thereby easing symptoms.
Preclinical studies in lab-grown cells and mouse models of autoimmune diseases showed S-1117 quickly reduced levels of IgG antibodies, an effect that was sustained over time. It also disrupted the ability of memory B-cells, immune cells that produce antibodies, to further mount an immune response.
The ongoing Phase 1 clinical study has two parts. First, adults will be randomly assigned to a single ascending dose of S-1117 or a placebo, given as an injection into a vein or under the skin. In the second part, adults will receive multiple ascending doses of S-1117 or a placebo.
Along with monitoring for side effects, researchers will measure how much S-1117 reaches the bloodstream, how quickly the therapy is eliminated from the body, how much it reduces IgG antibody levels, and how it affects memory B-cells. They’ll also check for antibodies against S-1117.
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