Targeting the $100 Billion Market: Insilico Medicine Nominates AI-driven Novel PCC ISM9528 for Pain Management

• AI-Driven New Mechanism Discovery: Targeting an undisclosed novel mechanism empowered by PandaOmics, the PCC ISM9528 offers a potential first-in-class, brain-penetrant, non-opioid solution for pain management.
• Superior Therapeutic Profile: In preclinical studies, ISM9528 demonstrated superior efficacy compared to the standard of care, along with a favorable safety profile as an oral treatment, and promising DMPK properties.
• Proven Reproducibility and Scale: As Insilico's 31st PCC nominated since 2021, ISM9528 further validates the capabilities of Insilico's proprietary Pharma.AI platform to consistently accelerate and empower drug R&D innovation.

CAMBRIDGE, Mass., July 22, 2026 /PRNewswire/ -- Despite the widespread availability of analgesics, pain management remains one of the most significant and pervasive challenges in modern medicine, with more than 20% of the global population suffering from chronic pain, especially chronic neuropathic pain characterized by central sensitization. However, the standard of care currently continues to rely heavily on opioids and NSAIDs, which are limited by inadequate efficacy, gastrointestinal toxicity, and the serious risks of dependence and addiction, calling for novel, effective, non-addictive, brain-penetrant analgesics.

Insilico Medicine ("Insilico", HKEX:3696), a clinical-stage, generative AI-driven drug discovery company, is addressing this critical unmet need by using AI to uncover novel biological mechanisms and develop innovative therapies. The company recently announced the nomination of ISM9528 as a Preclinical Candidate Compound (PCC) for pain management. Identified by PandaOmics, ISM9528 is a potential first-in-class, brain-penetrant, orally available inhibitor of Target Z that offers a novel, non-opioid treatment approach by acting on a previously unexplored biological mechanism. Notably, this marks the 31st PCC nominated by Insilico since 2021, further validating the company's AI-driven R&D capabilities.

"To see a non-opioid candidate outperform morphine in preclinical models is an unprecedented milestone, perhaps one of the most remarkable and unexpected results in our company's history, a result of frontier AI, human ingenuity and scientific serendipity." says Alex Zhavoronkov, PhD, Founder, CEO, and CBO of Insilico Medicine. "Target discovery for highly complex human mechanisms like chronic pain and migraine historically takes over a decade, but PandaOmics precisely mapped this pathway, driving us to our 31st PCC since 2021. By understanding the biology behind, we are not only addressing pain management, but moving one step closer to our ultimate ambition: decoding the biology of aging through our dual-purpose strategy."

To find a new path forward for pain management, the team leveraged PandaOmics, Insilico's AI engine for identification and prioritization of therapeutic targets. By analyzing massive datasets of omics, textual and multimodal data, PandaOmics helped the team uncover a new pain-related pattern, highlighting the potential of Target Z in Insilico's current portfolio, a novel target not systematically linked to pain management before, and driving their attention to a compound they had already developed.

Subsequent bioinformatics analyses of human and animal model data showed high expression of Target Z in pain-related cell types, strengthening the team's confidence to advance into wet lab testing. Moving swiftly into in vivo validation, The research utilized specialized mice models to imitate human pain mechanisms, demonstrating robust, dose-dependent pain management efficacy, with potential comparable or surpassing current solutions, including morphine.

Following target validation, the team aimed at brain-penetrant properties and a balance between efficacy and safety, deploying Chemistry42, Insilico's generative chemistry platform compassing 40+ selective models integrated into several affiliated applications to re-generate compounds with optimized selectivity and ADMET properties for pain indication. After iterative cycles of AI generation, human feedback and refinement, ISM9528 was selected as the lead compound for the project.

"The nomination of ISM9528 as the 31st drug candidate of Insilico validates the reproducibility and precision of our end-to-end AI platform," says Feng Ren, PhD, Co-CEO and CSO of Insilico Medicine, "Featuring both a novel mechanism of action and a highly distinct chemical structure, ISM9528 delivers superior efficacy and a favorable safety profile, with promising brain penetrant traits. Looking ahead, we are confident that our continuous integration of generative AI and automation will set new standards, deliver solid proof of concept, and introduce real-world clinical benefits for patients."

In preclinical studies, ISM9528 demonstrated superior efficacy compared to standard of care in validated models of acute postsurgical pain and neuropathic pain, as an oral treatment. Moreover, comprehensive in vitro and in vivo safety screenings across multiple panels and animal models confirmed exceptional safety properties, while rapid systemic absorption and excellent blood-brain barrier permeability support a favorable DMPK profile.

In the Spinal Nerve Ligation (SNL) rat model for neuropathic pain, ISM9528 dose-dependently restored mechanical allodynia. The middle dose delivered a significant analgesic effect across all time points up till 6h post dosing, which was comparable to Pregabalin, a standard of care for pain at similar dose level.

In the postsurgical acute pain model, in addition to the dose dependent efficacy, ISM9528 demonstrated a rapid-acting efficacy at 0.5-hour post-dosing outperforming the equivalent dose of Pregabalin.

"There is a tremendous unmet need for non-opioid pain medications, and the preclinical data for ISM9528 is quite promising," says Carol Satler, MD, PhD, Senior Vice President for Clinical Development, Non-Oncology, Insilico Medicine, "This is what we call a 'Eureka' moment, the kind of discovery that completely changes the landscape of how we treat patients. We are fast-tracking this exciting program toward clinical trials in 2027, driven to deliver a medicine that will genuinely transform patient care."

As an AI-native biotechnology company, Insilico is redefining the efficiency of preclinical drug development through its advanced AI and automation platform, setting a new standard for the industry. While traditional early-stage drug discovery typically takes 2.5 to 4 years, Insilico has consistently reached preclinical candidate (PCC) nomination in an average of just 12 to 18 months, with only 60 to 200 molecules synthesized and tested per program. Since 2021, the company has nominated 31 PCCs, 13 of which have received IND approval or clearance.

While expanding the practical applications of its technology in drug discovery and life science research, Insilico is also continuously enhancing the performance of its AI platform. Drawing on extensive experience and datasets from its training platform, the company has distilled thousands of benchmarks and integrated them into MMAI Gym. Serving as both a "trainer and benchmark" for scientific AI, MMAI Gym enables organizations to train models for domain-specific reasoning while rigorously evaluating their performance on real-world tasks, advancing the path toward pharma superintelligence. To date, Human Longevity and Liquid AI have collaborated with Insilico, joining as partners of MMAI Gym.

About Insilico Medicine

Insilico Medicine is a pioneering global biotechnology company dedicated to integrating artificial intelligence and automation technologies to accelerate drug discovery, drive innovation in the life sciences, and extend healthy longevity to people on the planet. The company was listed on the Main Board of the Hong Kong Stock Exchange on December 30, 2025, under the stock code 03696.HK.

By integrating AI and automation technologies and deep in-house drug discovery capabilities, Insilico is delivering innovative drug solutions for unmet needs including fibrosis, oncology, immunology, pain, and obesity and metabolic disorders. Additionally, Insilico extends the reach of Pharma. AI across diverse industries, such as advanced materials, agriculture, nutritional products and veterinary medicine.

For more information, please visit www.insilico.com 

SOURCE Insilico Medicine