In a landmark advancement poised to redefine therapeutic approaches for chronic fibrotic diseases, Professor Enrico Petretto and his team at Duke-NUS Medical School have secured a pivotal US$1.5 million award from 65LAB to accelerate the development of first-in-class antifibrotic therapies targeting lung and kidney fibrosis. These debilitating conditions, characterized by excessive scar tissue formation that progressively impairs organ function, have long resisted effective treatment due to their complex underlying biology and limited druggable targets. Leveraging a sophisticated systems genetics platform augmented by cutting-edge artificial intelligence (AI) and the nascent power of quantum computing, this initiative epitomizes a new paradigm in precision drug discovery designed to unlock molecular culprits driving fibrosis and facilitate the development of potent small-molecule inhibitors.
Fibrosis represents an escalating global health challenge, with idiopathic pulmonary fibrosis (IPF) affecting roughly one in 10,000 individuals in the Asia-Pacific region and chronic kidney disease projected to burden one in every four Singapore residents by 2035. The pathological hallmark involves the progressive deposition of extracellular matrix components, culminating in irreversible tissue remodeling and organ failure. Professor Petretto’s research specifically hones in on the WWP2 gene, previously identified as a pivotal regulator of fibrotic cascades across multiple organs including the lungs, heart, and kidneys. The inhibition of WWP2 demonstrates a remarkable protective effect on tissue architecture, offering a promising therapeutic target previously unexploited by conventional drug discovery methodologies.
At the core of this ambitious project is the Systems Genetics platform—a state-of-the-art integrative framework synergizing computational biology, genomic datasets, and increasingly sophisticated AI algorithms capable of executing high-throughput in silico screening. This computational prowess enables the interrogation of over 15 billion molecular entities, vastly outstripping the capabilities of traditional biochemical screening and allowing for the efficient and precise identification of candidate compounds with optimal binding characteristics and inhibitory potential against fibrosis-driving gene products. Notably, the platform’s evolution now includes exploratory integration with quantum computing technologies, which offer unparalleled advantages in processing complex molecular interactions at scales and speeds unattainable by classical computation.
This multifaceted approach is bolstered by a strategic partnership with 65LAB—a consortium of global investors and life science leaders including ClavystBio, Leaps by Bayer, Lightstone Ventures, Polaris Partners, and Evotec. Established to bridge the gap between early-stage academic innovation and commercial biotech ventures in Singapore, 65LAB provides not only funding but also venture-building expertise through its Expert-in-Residence program. This targeted support ensures that promising discoveries, such as Professor Petretto’s drug discovery pipeline, can transition smoothly from conceptual validation to therapeutic reality while fostering an entrepreneurial ecosystem that nurtures biotechnology startups dedicated to addressing pressing global health needs.
Complementing the substantial 65LAB award is an additional US$390,000 investment from Duke-NUS’ LIVE Ventures incubator, which specializes in shepherding early-stage innovations towards commercialization. The dual infusion of financial and strategic resources reflects a well-orchestrated ecosystem designed to overcome traditional bottlenecks in drug development—from target validation through to preclinical testing and eventual clinical trials. This collaboration underscores Singapore’s ambition to become a hub for high-impact biomedical innovation, supporting academic discoveries with the infrastructure and expertise necessary to navigate complex regulatory and market landscapes.
The scientific rationale behind targeting WWP2 and related pathways emerges from rigorous preclinical studies demonstrating at least a 50 percent reduction in fibrotic tissue scarring following treatment with the novel small-molecule inhibitors identified through the Systems Genetics platform. These results highlight the promise of a mechanistically targeted approach that interrupts the pathological signaling cascades driving fibrosis rather than merely alleviating symptoms. By focusing on gene activity modulation, the therapeutic candidates aim to effectively halt or reverse the progression of tissue scarring, thereby preserving organ function and dramatically enhancing patient outcomes.
A key driver of this initiative’s success has been the leadership of interdisciplinary research efforts combining computational biology, genetic analysis, and pharmacology. Dr. Chen Huimei, co-Principal Investigator and Principal Research Scientist, emphasizes how the integration of AI algorithms enables the team to widen the pool of potential drug candidates and refine the precision of their target screening pipelines. This computational synergy accelerates discovery cycles and enhances the likelihood of identifying molecules with intrinsic drug-like properties and reduced off-target effects, ultimately streamlining the translational trajectory from bench to bedside.
Looking ahead, the project envisions extensive collaboration with industry partners and clinical researchers to rigorously test and develop these innovative inhibitors into clinically viable drugs. The translation pathway will involve robust pharmacokinetics, safety profiling, and efficacy studies across relevant animal models of organ-specific fibrosis before entering human clinical trials. Duke-NUS’ Centre for Technology and Development will play a vital role in safeguarding intellectual property through strategic patent filings, safeguarding the commercial viability of novel molecular entities identified through this breakthrough platform.
The 65LAB award not only validates the groundbreaking nature of Professor Petretto’s Systems Genetics pipeline but also exemplifies the powerful impact of synergistic ecosystems that combine the strengths of academic ingenuity, AI-driven methodologies, and investment acumen. Experts such as 65LAB Joint Steering Committee Chair Dr. Pei-Sze Ng assert that this initiative embodies a blueprint for scientists and investors to collaboratively accelerate groundbreaking drug discovery while fueling Singapore’s aspirations as a global biotech innovation hub. Similarly, Duke-NUS Vice-Dean for Innovation and Entrepreneurship, Associate Professor Christopher Laing, underscores how the project’s AI-driven target discovery approach promises to generate a pipeline of investible opportunities well beyond fibrosis.
The success of this award follows a precedent set by earlier recipients such as Associate Professor Lena Ho, who also received 65LAB support for her pioneering work in microprotein therapeutics targeting chronic inflammation. Collectively, these initiatives demonstrate the rising momentum of Singapore’s biomedical research landscape in addressing urgent clinical needs through innovative science and strategic partnerships. They also signal a shift towards data-intensive, AI-enhanced platforms that capitalize on computational advances to expedite drug discovery timelines that have traditionally spanned decades.
Ultimately, this groundbreaking endeavor stands as a beacon of hope for millions suffering from fibrotic diseases worldwide, opening avenues toward therapies that could mitigate irreversible organ damage and transform long-term clinical outcomes. It epitomizes the convergence of multidisciplinary expertise, technological innovation, and visionary investment, setting the stage for a new era of targeted, efficient, and scalable drug discovery and development within Singapore’s vibrant biomedical ecosystem and beyond.
Subject of Research: Antifibrotic drug discovery targeting lung and kidney fibrosis using systems genetics, AI, and quantum computing.
Article Title: Breakthrough Antifibrotic Therapies Emerge from AI-Driven Systems Genetics Platform at Duke-NUS
News Publication Date: 13 August 2025
Web References:
- Duke-NUS LIVE Ventures: https://www.duke-nus.edu.sg/innovation/teams/live-ventures
- Duke-NUS Centre for Technology and Development: https://www.duke-nus.edu.sg/cted
- 65LAB official site: https://65lab.sg/
- Professor Enrico Petretto’s profile: https://www.duke-nus.edu.sg/directory/detail/petretto-enrico-giuseppe
References:
Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, Patel H, Kreuter M. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respiratory Research. 2021 Dec;22:1-0.
Image Credits: Chen Huimei, Duke-NUS Medical School
Keywords: Clinical medicine, Clinical studies, Antifibrotic therapies, Lung fibrosis, Kidney fibrosis, Systems genetics, Artificial intelligence, Quantum computing, Drug discovery, Duke-NUS, 65LAB, Biotechnology venture creation
