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 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. This work is supported by large chemical libraries (including class targeted scaffolds and comprehensive clinical stage molecules), automated screening and imaging systems and compound management infrastructure.
The design and development of tissue-specific therapies, including antibody-drug conjugates , bispecific antibodies, and engineered cell therapies, has gained considerable interest for the treatment of cancer based on the ability to greatly improve safety while maximizing therapeutic benefit. Scientists at Calibr are committed to innovating the next generation of tissue-targeted therapies for cancer, as well as extending these principles to non-oncology indications, such as cystic fibrosis, metabolic disease, and autoimmunity. . Calibr has developed 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. Calibr is also using novel protein engineering strategies to target cytotoxic T cells, immunomodulators, and phagocytic agents to specific cell types and protein aggregates. Finally, 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.
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.