Dosing of ISM001-055, Oral IPF Therapy, Begins in Phase 1 Trial

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Dosing has begun in healthy volunteers in a Phase 1 clinical trial of ISM001-055, a small molecule potential treatment of idiopathic pulmonary fibrosis (IPF) developed using an artificial intelligence (AI) platform, Insilico Medicine announced.

Up to 80 adults in this study  (NCT05154240), currently enrolling at its one New Zealand site, will be given single and multiple ascending doses of ISM001-055 to determine its safety, tolerability, and pharmacokinetics — movement into, through, and out of the body — as an oral treatment.

A previous trial of intravenous (into-the-vein) microdoses of ISM001-05 in eight healthy volunteers in Australia identified a safe microdose with a favorable pharmacokinetics profile.

“I am delighted that Insilico’s AI-powered, end-to-end anti-fibrotic program just passed [a] microdose study in humans and has entered Phase I,” Michael Levitt, PhD, a member of Insilico’s scientific advisory board and 2013 Nobel Laureate in Chemistry, said in a press release.

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Pharma.AI is the name given to Insilico’s artificial intelligence-driven drug discovery and development platform. The process starts with identifying a target — a specific molecule that plays a role in the disease. This is done using PandaOmics, the deep learning engine part of Pharma.AI that uses a set of algorithms to analyze a pool of data and rank candidate targets. These targets are then narrowed to the one showing the best potential.

The platform then uses Chemistry42 to virtually ‘sketch’ new small molecules directed against the selected target.

“Modern deep learning technologies enable us to perform target identification using longitudinal biological data from healthy subjects and make inferences into a variety of diseases. This was the guiding principle for our anti-fibrotic program starting with identifying targets that may play a role in both aging and disease,” said Alex Zhavoronkov, PhD, founder and CEO of Insilico.

“It gives me great pleasure to announce that we have … entered the full Phase I clinical trial with a once-a-day oral dose of our ISM001-055 anti-fibrotic where the target was identified using AI and the molecule was designed using AI, meaning it is AI-discovered and AI-designed,” Zhavoronkov added.

The two-part, double-blind and placebo-controlled Phase 1 trial will test escalating doses of the oral treatment. In part one, five groups of volunteers will test single doses of increasing strength; in part two, five other groups will test multiple ascending doses given over 10 days. The goal is to determine the highest safe and tolerable dose — that which does not cause troubling side effects — and to establish a recommended dose for future Phase 2 trials.

Trial researchers will also investigate whether food affects ISM001-055’s pharmacokinetics. The trial is expected to conclude in February 2023.

“We are committed to taking advantage of AI-driven drug discovery to rapidly advance the development of innovative therapeutics for unmet medical needs, especially in the areas of fibrosis, oncology, immunology, and neurology, and initiating this phase I study demonstrates the power of our AI platform in achieving that,” said Feng Ren, PhD, chief science officer of Insilico.