Calibr is unique among research institutes in possessing end-to-end preclinical discovery capabilities. Scientists at Calibr develop and implement complex, cell-based high-throughput screens to discover novel chemical matter; rapidly explore derivatives to identify suitable lead compounds for full biological characterization in cells and animal models of disease; and deploy iterative medicinal chemistry and pharmacology resources to optimize efficacy, safety, and drug-like properties, ultimately providing preclinical candidate molecules suitable for IND-enabling activities and clinical studies with a development partner. Moreover, Calibr is highly proficient in using these biologically active small molecules to discover new biological mechanisms involved in cellular and disease processes.
Antibody-drug conjugates have gained considerable interest in oncology for their ability to enhance efficacy and improve safety of cytotoxic chemotherapeutics. However, the concept of tissue-targeted drug delivery has not yet been exploited in non-cancer indications. Calibr uses innovative, modular synthetic approaches to generate tissue-targeted drugs, exploiting both receptor-mediated uptake, as well as rational modulation of physiochemical properties that control absorption and distribution to restrict a drug’s action to tissues of interest. By directing drugs to the liver, the lung, and various immune cells, Calibr is broadening the utility of this therapeutic paradigm not only in cancer, but also to various metabolic, respiratory, and inflammatory diseases.
The potency and specificity of proteins and peptides make them attractive pharmaceutical agents, but poor stability and short plasma half-lives render them inconvenient or intractable for chronic therapy. Calibr scientists have pioneered new platform technologies to improve the efficacy, pharmacokinetics, and convenience of therapeutic proteins and peptides. One approach builds on our ability to rationally engineer into the antibody scaffold selective receptor agonist and antagonist activities, resulting in biologics with enhanced pharmacokinetics and physicochemical properties. Another approach uses a repertoire of synthetic modifications to fortify helical peptides against degradation and rapid clearance, creating peptide drugs with extended half-lives, as well as sufficient potency and stability to be administered via novel routes of delivery. In addition, we have developed new library based strategies to identify endogenous peptides and proteins with novel disease modifying biological activities.
The ability of the adaptive immune system to eliminate cancer cells has led to a new paradigm in clinical oncology wherein T cells are engineered with exquisite anti-tumor capacity. Calibr scientists are taking two distinct approaches to T cell-based therapies. The first uses recombinantly expressed antibodies and semi-synthetic methods to generate bispecific antibodies that eliminate malignant cells with high potency and selectivity. The second employs genetically engineered chimeric antigen receptor T cells (CAR-Ts) which boast rapid, durable, and potent anti-tumor responses. Calibr’s unique approach to CAR-T therapy is based on a platform that couples CAR-T cells with bifunctional ‘switch’ agents to enhance the safety, versatility, and temporal control of this therapeutic modality