From Bench to Bedside
Treadwell is a science-first organization solely focused on developing novel therapeutics for unmet needs in cancer. With a robust set of internal discovery tools and capabilities at our Toronto based R&D hub, we translate innovative scientific ideas and therapeutic targets into practice changing medicines. We are currently advancing three clinical stage, first-in-class, internally developed small molecules in a variety of solid and hematologic malignancies.
- CFI-400945 is an inhibitor of Polo-Like Kinase 4 or PLK4, a target identified by Treadwell scientists. PLK4 is an enzyme necessary for cancer cells to divide and multiply in the presence of increased chromosome count, is a key regulator of centriole duplication. PLK4 is frequently overexpressed in cancer cells and is associated with adverse survival outcomes. Inhibition of PLK4 has been shown to exacerbate genomic instability in cancer cells, forcing cell death. CFI-400945 has shown promise in multiple investigator initiated studies across a spectrum of aggressive cancers, including high risk AML. A company sponsored, multi-site global study in Leukemia (TWT-202) is ongoing.
- CFI-402257 is a potent and selective inhibitor of TTK/Mps1 (Tyrosine Threonine Kinase/monopolar spindle 1), another target identified by Treadwell scientists. TTK is a conserved dual-specificity protein kinase, an enzyme essential for the maintenance of genomic stability during cell division. It is a critical regulator of the spindle assembly checkpoint (SAC), and its over–expression correlates with high grade in tumors and poor patient outcome. Inhibition of TTK allows cancer cells to progress through mitosis in the presence of misaligned chromosomes, resulting in eventual cell death. CFI-402257 has shown particular clinical utility in certain subsets of breast cancer in investigator sponsored studies, with a global company sponsored study in planning phase.
- CFI-402411 is a novel, orally bioavailable inhibitor of HPK1 (Hematopoietic Progenitor Kinase 1, aka MAP4K1) discovered through an intensive medicinal chemistry effort and developed by Treadwell scientists. HPK1 is a kinase enzyme and a critical negative regulator of immune cell activation, antigen presentation, and T cell responses to immunosuppressive factors. Inhibition of HPK1 has been shown to activate T cells, B cells, and dendritic cells. Preclinical studies have demonstrated the promise of CFI-402411 as a potential monotherapy in both solid and hematological cancers, and in combination with existing checkpoint inhibitors. It is our hope that CFI-402411 will provide a novel immuno-oncology strategy strongly differentiated from current therapies. We are currently in the early stages of a global, multi-site company sponsored trial (TWT-101) studying CFI-402411 in advanced solid tumors as a monotherapy and in combination with PD1 blockade.
A Robust Preclinical pipeline
While pursuing these early successes, our research continues to further identify previously unexplored targets of therapeutic intervention for the most aggressive of cancers.
We have a number of internally developed undisclosed Biologic programs (antibodies and soluble receptor traps) that have shown compelling pre-clinical efficacy. These programs represent novel Immuno-oncology targets with a myeloid restricted expression profile.
We are also developing a novel approach to autologous, TCR transgenic T cell therapy based on our robust internal TCrypt platform. Using this novel tool, we can quickly and in a high throughput manner, identify therapeutically relevant TCRs for therapy. We believe our approach can address patient populations underserved by current approaches in a variety of different solid and hematologic malignancies where there is an unmet need.