Researchers from artificial intelligence (AI) drug developer Insilico Medicine and two partner institutions have published a study concluding that its lead candidate ISM001-055 is the first to show anti-aging properties and that its mechanism of action offers a promising therapeutic approach for treating age-related diseases.
ISM001-055 was shown to have attenuated cellular senescence through the suppression of various aging processes, thus showing potential as a senomorphic drug. Senomorphics are a class of drugs that targets the senescence-associated secretory phenotype (SASP) of senescent cells, which have stopped dividing and accumulate in tissues as people age, thus are considered to play a role in aging and age-related diseases.
The study also showed ISM001-055 to function as a senomorphic agent, modulating the behavior of senescent cells rather than eliminating them. ‘055 not only matched, but also surpassed the FDA-approved sirolimus, formerly rapamycin—sold by Pfizer as Rapamune® and by several other companies as generic versions—in two key areas:
- Reduction of SASP factors: ISM001-055 was more effective than rapamycin in decreasing the secretion of pro-inflammatory cytokines and other SASP components, which are linked to tissue dysfunction and age-related pathologies.
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- Restoration of cellular function: Cells treated with ISM001-055 exhibited a more pronounced return to youthful functionality compared to those treated with rapamycin, indicating superior rejuvenative properties.
ISM001-055 is an internally developed Insilico drug candidate developed using generative AI. The drug is designed to treat idiopathic pulmonary fibrosis (IPF) by targeting Traf2- and NCK-interacting kinase (TNIK), a serine/threonine kinase whose activation plays a crucial role in cellular processes that include signal transduction pathways essential for fibrosis development.
In inhibiting TNIK, ISM001-055 reduced the activation of the TGF-β and Wnt/β-catenin pathways, which are involved in SASP regulation. This enabled ‘055 to suppress pro-inflammatory cytokine production while preserving senescent cells that may still serve beneficial functions, such as in tissue repair and tumor suppression.
“The strong evidence that TNIK plays a role in aging and senescence could influence Insilico to expand the development of ISM001-055 beyond fibrosis and into broader geroprotective and anti-aging applications,” Insilico founder and CEO Alex Zhavoronkov, PhD, told GEN Edge.
Insilico’s future plans for INSM001-055 are undisclosed.
Implicating TNIK in aging
“This study further strengthens the potential of INS018_055 as a longevity therapeutic by implicating TNIK in the cellular senescence hallmark of aging,” the researchers concluded, using the drug candidate’s former name, in “AI-Driven Robotics Laboratory Identifies Pharmacological TNIK Inhibition as a Potent Senomorphic Agent,” a study published in Aging and Disease. The Insilico researchers were joined by investigators from China’s Suzhou Hospital of Nanjing Medical University, as well as from the Buck Institute for Research on Aging.
“This research highlights the novel role of TNIK in cellular senescence and new senomorphic applications for INS018_055, in addition to its anti-fibrotic properties that may inform future efforts to treat age-related diseases,” the researchers added.
ISM001-055 has generated positive results in a “Phase 0” microdose trial (ACTRN12621001541897) and two Phase I clinical trials, one conducted in New Zealand (NCT05154240) and the other, in China (CTR20221542)—as well as a Phase IIa trial conducted across 21 sites in China (NCT05938920). That study’s secondary efficacy endpoint showed dose-dependent improvements in forced vital capacity (FVC), with the largest improvement observed in the 60 mg QD [once daily] cohort.
Insilico is working to validate findings from these studies through a parallel Phase IIa trial (NCT05975983) now enrolling patients in the United States. The study is projected to enroll a total of 60 patients and achieve primary completion in February 2026.
However, the results detailed in the latest paper came not from these clinical trials but from a study Insilico carried out at its AI-based, sixth-generation robotics laboratory in Suzhou, China, which according to the company, allowed for increased validation and consistency across experiments.
“Insilico conducted this separate study using its AI-driven robotics lab to explore the senomorphic potential of ISM001-055 beyond its known anti-fibrotic effects,” Zhavoronkov said. “The robotic study provides high-throughput, automated, and AI-driven analysis of cellular responses, allowing for a detailed mechanistic understanding of how ISM001-055 impacts cellular senescence. This approach enables the identification of molecular pathways, aging biomarkers, and transcriptional changes in response to treatment.”
Reducing inflammatory cytokines
Researchers found that ISM001-055 primarily attenuates SASP by reducing inflammatory cytokines such as IL-6, IL-8, IL-1A, and IL-1B. ‘055 also attenuates extracellular matrix (ECM) remodeling, preventing excessive fibrosis and tissue dysfunction; as well as TGF-β signaling, a major driver of fibrosis and senescence-associated inflammation.
In addition to reducing inflammation, results of attenuation included improving mitochondrial function, and outright increasing of healthy years or “healthspan.”
Which effects is Insilico most interested in seeing?
“Improving mitochondrial function and increasing healthspan are incredibly important and a major goal,” Zhavoronkov explained. “The most immediate translational impact comes from mitigating chronic inflammation and ECM remodeling, which are major drivers of aging-related diseases.”
Zhavoronkov added that Insilico will continue focusing on reducing inflammation and SASP, since they contribute directly to multiple age-related diseases, including fibrosis and chronic inflammatory conditions.
“Insilico will continue to confirm the findings by conducting more validating studies to ensure that the senomorphic effects observed in cellular models translate into whole-organism benefits. As progress continues, additional trials targeting aging-related diseases and conditions driven by senescence may be launched,” Zhavoronkov said.
The researchers acknowledged they will need to collect additional data to support ISM001-055’s use for anti-aging therapy in clinical settings. According to Zhavoronkov, potential ways to further collect this data may include:
- Animal model studies intended to validate ‘055’s effects on senescence and aging in vivo
- Biomarker studies designed to identify changes in aging-related molecular markers in treated organisms
- Potential expansion of clinical trials to evaluate its effects on age-related diseases beyond IPF
- AI-driven modeling to refine target selection and optimize dosing strategies for anti-aging effects
In a paper published in March in Nature Biotechnology, a team of 30 researchers led by Zhavoronkov detailed how they used generative AI to discover INS018_055, with a novel target discovered by Insilico’s target identification engine, PandaOmics, and a novel molecular structure designed by its generative chemistry engine, Chemistry42. Both are specific-function platforms within the company’s AI platform, Pharma.AI.
ISM001-055 is Insilico’s first wholly owned program in which AI was used to identify a novel target and generate novel small molecules through Pharma.AI. Insilico won the FDA’s first Orphan Drug Designation for an AI drug in 2023.