Grant: CCI Applied Research and Development Grants

Cancer represents a pressing global health challenge and despite advancements in treatment, the limitations of traditional therapies underscore the urgent need for innovative therapies that are both effective and tolerable. 9Bio Therapeutics proposes a transformative approach, leveraging an AI-assisted protein engineering platform to develop precision oncology therapeutics tailored to the unique biochemical environment of tumors to develop innovative therapeutics with enhanced specificity, addressing longstanding challenges in tolerability and safety. 9Bio’s approach begins with the recognition that tumors exist within specific microenvironments characterized by oxygen depletion, acidity, and accelerated metabolic activity. These conditions differ significantly from those of healthy tissues, creating opportunities for the development of therapies that target cancer cells with minimal off-tumor effects. Central to the proposal is the development of tumor-specific therapies that minimize systemic toxicity. By introducing histidine residues into the antibody structure, these therapies achieve selective binding of their targets in acidic conditions within the tumor. One focus is the engineering of an interleukin-9 variant, a cytokine with demonstrated anti-tumor activity in preclinical models yet with a concerning tolerability profile. 9Bio’s strategy generates a novel therapeutic to enhance its affinity for its receptor in acidic tumor environments while ablating binding in the healthy periphery. This novel therapy holds promise for harnessing underexplored immune mechanisms such as mast-cell activation, providing a unique mechanism of tumor control. Another key objective is the development of advanced antibody-drug conjugates. By engineering new antibodies that bind preferentially in tumor-specific environments, 9Bio aims to overcome limitations associated with toxicity related to partial tumor antigen expression in healthy tissues. Proof-of-concept studies will evaluate these therapeutics in cell-based and in vivo models, establishing their potential to improve tumor targeting and overcome current limitations in cancer treatment. By addressing bioavailability, tolerability, and effectiveness, 9Bio aims to broaden the availability of life-saving cancer therapies to a wider range of patients, including those who have previously been unable to benefit from existing treatments due to safety or tolerability concerns.