Key Findings
Constructive Bio is pioneering a groundbreaking approach to enable oral bioavailability for peptide therapeutics previously restricted to injectable administration, by incorporating unnatural amino acids into their designs. The company is building a pipeline of oral peptide drugs based on this innovative technology, while simultaneously pushing forward with antibody-drug conjugate (ADC) programs utilizing genetic code expansion.
Technical/Clinical Details
The company’s oral peptide therapeutics overcome the long-standing challenges of peptide degradation in the gastrointestinal tract and poor absorption due to their size. This is achieved by introducing unnatural amino acids into the molecular structure, which imparts novel membrane permeability properties. These modified peptides can efficiently traverse the intestinal epithelial cells to reach systemic circulation, significantly enhancing patient convenience and improving treatment adherence. Concurrently, Constructive Bio is leveraging genetic code expansion technology for its ADC programs. This method allows for the site-specific incorporation of unnatural amino acids onto antibodies, enabling more precise and uniform conjugation of drug payloads. By tightly controlling the drug-to-antibody ratio (DAR), the company aims to optimize the therapeutic index (the balance between efficacy and safety), developing next-generation ADCs with superior efficacy and reduced side effects compared to existing ADCs.
Background & Context
Peptide drugs offer high specificity and potent pharmacological effects but have long faced challenges with oral administration due to their susceptibility to digestive enzymes and low permeability across the gastrointestinal epithelium. While the success of oral semaglutide demonstrated a path forward, its specific formulation is not universally applicable. Constructive Bio’s approach, using unnatural amino acids, offers a more versatile tool to address this challenge across a broader range of peptides. In the ADC field, rapid advancements have been made, but improving drug conjugation uniformity and therapeutic index remains key for the next wave of breakthroughs. Genetic code expansion is recognized as a promising technology to enable such precise ADC engineering.
Strategic Significance & Outlook
Constructive Bio’s pipelines in oral peptides and genetic code-expanded ADCs hold the potential to make a significant impact in drug delivery systems and novel therapeutic modalities, respectively. If oral peptide therapeutics become widely available, they could dramatically improve the quality of life for patients with chronic conditions requiring peptide injections, such as diabetes, obesity, and inflammatory diseases. Furthermore, optimized ADCs could provide more effective and safer options in cancer treatment, improving outcomes in areas with high unmet medical needs. The company’s technology is poised to expand the frontiers of pharmaceutical development and offer new treatment choices to patients, with upcoming clinical development progress being keenly watched.
Source: https://constructive.bio/cure/
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