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Recludix succeeded in drugging SH2 domains, a target class abandoned in the 90s, by integrating five modern technologies. This platform includes proprietary DNA-encoded libraries, machine learning, a selectivity tool, novel crystallography methods, and a pro-drug approach to ensure cell permeability, demonstrating the complex approach needed for modern drug discovery breakthroughs.
Recursion's CEO outlines a two-pronged pipeline strategy. The first prong uses phenomics to uncover novel biological insights for new targets, like their FAP program. The second uses their AI-driven small molecule design platform to improve the therapeutic index for known but historically 'hard-to-drug' targets, like CDK7. This balanced portfolio approach de-risks development by leveraging different strengths of their end-to-end platform.
The company focuses on disease-specific 3D protein conformations, which exposes new binding sites (epitopes) not present on the same protein in healthy cells. This allows for highly selective drugs that avoid the toxicity common with targets defined by genetic sequence alone.
Traditional drug discovery separates finding a 'hit' from the long process of optimizing it into a drug candidate. DenovAI's 'one-shot' platform builds in advanced features from the start, collapsing a multi-year, disjointed process into a single, efficient design phase.
Instead of relying on finding novel targets, a key strategy in neuropsychiatry is to revisit failed compounds that showed efficacy signals. Companies use modern chemistry and delivery to engineer solutions that separate efficacy from the historical liabilities that halted development, turning past failures into new opportunities.
Pathways like integrins have long been of interest but lacked effective therapeutic approaches. The advent of new technologies, such as antibody-drug conjugates and checkpoint inhibitors, has created opportunities to re-explore these older targets with potent, modern drugs, breathing new life into decades-old research.
Recludix posits that for chronic diseases, inhibiting a protein's specific function is superior to complete degradation. Degrading a protein can disrupt its other essential roles (e.g., mitochondrial function), leading to unnecessary toxicity. Inhibition offers a more targeted, reversible approach with a potentially better long-term safety profile.
Instead of screening billions of nature's existing proteins (a search problem), AI-powered de novo design creates entirely new proteins for specific functions from scratch. This moves the paradigm from hoping to find a match to intentionally engineering the desired molecule.
ProPhet's strategy is to focus on 'hard-to-drug' proteins, which are often avoided because they lack the structural data required for traditional discovery. Because ProPhet's AI model needs very little protein information to predict interactions, this data scarcity becomes a competitive advantage.
Many innovative drug designs fail because they are difficult to manufacture. LabGenius's ML platform avoids this by simultaneously optimizing for both biological function (e.g., potency) and "developability." This allows them to explore unconventional molecular designs without hitting a production wall later.
Instead of developing another BTK kinase inhibitor, Recludix is creating an inhibitor for BTK's SH2 domain. The company believes this novel mechanism can overcome the efficacy and safety challenges that have limited kinase inhibitors in immunology indications, aiming for a best-in-class profile by targeting a different functional site on the protein.