Benefits of Miniaturized Drug Conjugates

Targeted drug conjugates – which link targeting agents to potent cell-killing payloads – have been a highly successful approach for creating effective cancer therapies while reducing the toxicity associated with non-targeted payloads.

  • The first generation of these biologic targeted drug conjugates are antibody drug conjugates (ADCs) based on the use of antibodies as the targeting agent, building on the breadth of recent antibody drug development in a variety of therapeutic settings. ADCs have been developed for both hematologic and solid tumors, and patients are already benefitting from these therapies in both settings. The specificity of the antibody coupled with the long circulation time allows the ADC to bind to the targeted tumor tissue and expose the cell to the potent cytotoxic payload. While ADCs have shown promise, there appear to be certain limitations in efficacy for their widespread use, notably in solid tumors or other cancers where penetration and efficacy have been elusive.
  • The small size of miniaturized drug conjugates overcomes one of the key biological barriers experienced with today’s targeted drug conjugates because they are designed to address the challenge of penetration into the dense solid tumor tissue. By using a targeting agent much smaller than an antibody, such as peptides, small molecules, or antibody fragments, miniaturized drug conjugates are able to rapidly penetrate into the tumor tissue. Particularly in solid tumors, miniaturized drug conjugates have attributes that allow them to effectively penetrate dense tumor tissue and associated extracellular matrix, resulting in unprecedented ability to therapeutically penetrate and target tumors. Yet, pharmacokinetic and biodistribution challenges have impacted miniaturized drug conjugates efficacy to date.
  • Tarveda’s innovative use of inherent miniaturized drug conjugate design features and/or nanoparticle incorporation to create Pentarins™ produces distinct therapeutic features. Traditionally, miniaturized drug conjugates as a drug class have faced a limitation of poor circulation time. By the intentional selection of appropriate targeting ligand, payload and optimized linker, Tarveda has demonstrated that it is possible to tune the pharmacokinetics and biodistribution of the Pentarins to achieve robust efficacy in solid tumors.

    Tarveda also recognizes that to achieve optimal efficacy with Pentarins, in certain instances, enhancement of the pharmacokinetics and biodistribution can be achieved through the application of tuning technologies. To date, other miniaturized drug conjugate developers have attached large polyethylene glycol polymers or used other similar strategies to improve the circulation times and pharmacokinetic properties of the conjugates; but doing so increases the size of the conjugates and adversely impacts the ability of these modified conjugates to penetrate solid tumors. By leveraging proprietary polymeric nanoparticle and other technologies developed by Tarveda, Pentarins avoid this tradeoff and retain the optimal properties of advantageous circulation time and tumor penetration. Tarveda has demonstrated that by incorporating Pentarins into intelligently designed nanoparticles, we can protect our Pentarins from rapid clearance and enable their distribution and accumulation in tumors through the leaky vasculature that is characteristic of most solid tumors.