Nobel Prize winner believes that a "real breakthrough" has been achieved, and the new drug developed by AI has been clinically verified for the first time
Jiefang Daily and Shangguan News reporter learned today from Insilicon Intelligence that this foreign company with its drug R&D center in Shanghai has achieved positive research results in the clinical trials of AI new drugs. The candidate new drug code-named ISM001-055 has achieved not only the primary research endpoint, i.e., drug safety verification, but also the secondary research endpoint, i.e., preliminary efficacy verification, in the Phase IIa clinical trial. It showed a dose-dependent efficacy trend in the "forced vital capacity", an indicator for evaluating the improvement of lung function in patients with idiopathic pulmonary fibrosis. This result provides the first conceptual verification for AI-driven drug development.
Dr. Michael Levitt, Nobel Prize winner in Chemistry, said: "This drug not only showed safety in Phase IIa clinical studies, but also showed efficacy, which means that artificial intelligence-driven drug discovery has made a real breakthrough."
Levitt spoke at the 2023 World Top Scientists Forum.
Idiopathic pulmonary fibrosis is a chronic scarring lung disease characterized by a progressive and irreversible decline in lung function. Due to its hidden onset and progression, most patients are diagnosed at an advanced stage, with a median survival of 3 years. Existing anti-fibrotic drugs can slow disease progression but cannot prevent or reverse the disease, and have significant adverse reactions.
As an AI-driven pharmaceutical company, Insilico Medicine has developed an "end-to-end" AI drug discovery platform that connects biology, chemistry, clinical medicine, etc. The platform's mature applications include the target discovery engine PandaOmics, the small molecule compound design engine Chemistry42, and the clinical trial results prediction engine InClinico.
Artificial intelligence drives the development process of anti-fibrosis TNIK inhibitors
Dr. Alex Zavoronkov, founder and CEO of Insilico Medicine, said that for idiopathic pulmonary fibrosis, the company's R&D team used omics and clinical data sets related to tissue fibrosis to train PandaOmics. This engine generates a list of potential targets through processes such as deep feature synthesis, causal inference, and new pathway reconstruction. Subsequently, PandaOmics' natural language processing model analyzed millions of text files covering text data such as patents, publications, R&D funds, and clinical trials, and deeply evaluated the novelty of these potential targets and their relevance to the disease, ultimately determining that TNIK is the most promising anti-fibrosis target.
After determining the target, the R&D team used the small molecule compound design engine Chemistry42 to generate innovative molecular structures based on structure-based drug design strategies. After multiple iterations of screening, they comprehensively considered the drug's solubility, physicochemical properties, toxicity and other parameters for optimization, and finally obtained the candidate molecule ISM001-055.
In March this year, the company published a paper in the top international scientific journal Nature Biotechnology, which introduced the whole process of using artificial intelligence platform to discover TNIK, a new target for the treatment of idiopathic pulmonary fibrosis, and using generative chemistry platform to design ISM001-055 molecule. The paper also disclosed the preclinical data and early clinical research results of this small molecule drug.
Zhavoronkov spoke at the 2023 World Top Scientists Forum.
According to reports, the Phase IIa clinical study of ISM001-055 was a randomized, double-blind, placebo-controlled trial that recruited 71 patients with idiopathic pulmonary fibrosis at 21 clinical research centers in China. Patients were randomly assigned to four parallel groups: 30 mg once a day, 30 mg twice a day, 60 mg once a day, and placebo. They were observed for 12 weeks. In August of this year, the clinical trial completed the follow-up of the last subject.
Preliminary studies have shown that ISM001-055 exhibits good safety at all dose levels, most of the adverse events related to treatment are mild, and no treatment-related deaths have been reported. In terms of the secondary endpoint, which is mainly measured by "forced vital capacity" to improve the patient's lung function, a dose-dependent efficacy trend was shown. Patients who received 60 mg of the drug once a day had the greatest improvement in "forced vital capacity."
Following these positive results, Insilico Medicine plans to discuss the design of a Phase IIb study with regulatory authorities to further investigate the therapeutic potential of ISM001-055 over a longer dosing period and in a wider patient cohort.