Targeted therapeutics, including antibody-drug conjugates ADCs, designed to  link targeted monoclonal antibodies, via a linker, to potent cell-killing payloads, have been a highly successful for creating effective cancer therapies.

Building on the breadth of recent antibody drug development in a variety of therapeutic settings for both hematologic and solid tumors, have benefited patients 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, some scientists are concerned about what appear to be limitations in efficacy for the widespread use of these novel agents.  They point to the complexity of  the development of ADCs for the treatment of patients with solid tumors where penetration and efficacy have, in many cases, been elusive.

…We take a novel approach to cancer therapeutics through our Pentarins™, which are potent and selective, miniaturized conjugates uniquely designed to penetrate deep into solid tumors, accumulate their payload, and cause cancer cell death…

Miniaturized-drug conjugates have been developed to overcome these key biological barriers and challenges.  As a novel, targeted approach, miniaturized-drug conjugates are designed to address the some of the challenges of penetration into the dense solid tumor tissue.


These novel, investigational agents use 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.

Especially in the treatment of solid tumors, these miniaturized drug conjugates have unique attributes that allow them to effectively penetrate dense tumor tissue and associated extracellular matrix, resulting in unprecedented ability to therapeutically penetrate and target tumors.  However, pharmacokinetic and biodistribution challenges have impacted the efficacy of these miniaturized drug conjugates. Furthermore, miniaturized drug conjugates, as a drug class, have also faced poor circulation time.

Overcoming limitations
To overcome the limitations of both antibody-drug conjugates and miniaturized drug conjugates, scientists at Tarveda Therapeutics developed a new class of potent and selective miniaturized drug conjugates with high-targeting capabilities for the treatment of solid cancer tumors. The innovative use of the features of miniaturized drug conjugates and nanoparticles resulted in the creation of Pentarins™, which have a high affinity for specific cell surface and intracellular targets and payload delivery deep into solid tumor tissue.

Comprised of a targeting ligand conjugated to a potent cell-killing agent through a chemical linker, Pentarins are designed to overcome the deficits of larger antibody-drug conjugates and small molecules that limit their therapeutic effectiveness against solid tumors. Together, the components of Tarveda’s Pentarins have distinct yet synergistic anticancer attributes: the small size of Pentarins allows for effective penetration and distribution into the tumor tissue, the ligand’s targeting ability allows for specific binding to tumor cells, the chemical linker is tuned to optimize the release of the potent, cell-killing payload inside the cancer cells for efficacy.

Lead compounds
The company’s lead drug candidate, PEN-221, targets the somatostatin receptor for treatment of patients with neuroendocrine and small cell lung cancers. The investigational agent contains a peptide ligand that is highly selective in targeting, and dependent on, the somatostatin receptor SSTR2. This somatostatin receptor is overexpressed on the surface of cancer cells in a variety of neuroendocrine cancers, including small cell lung cancer. By engineering PEN-221 with its modified peptide ligand, which is chemically linked in a unique and optimized fashion to a potent cell-killing payload, scientists at Tarveda where able to achieve the desired efficacy and pharmacokinetic and biodistribution attributes.

According to the developers, PEN-221 is just one example were the implementation of the Pentarin platform was optimized through a deep understanding of ligands to receptors, linker chemistries, and payloads. In preclinical studies, PEN-221 demonstrated deep tumor penetration with complete tumor regressions in multiple, hard to treat xenograft cancer models and has demonstrated superiority to the clinical standard of care, while a mixture of the unconjugated payload with the targeting agent shows no efficacy.

In addition, Tarveda is also advancing its HSP90 drug conjugate platform with PEN-866, which is a miniaturized drug conjugate that comprises an HSP90 ligand conjugated to SN-38, the highly-potent, active metabolite of irinotecan.

This week, the European Cancer Organization’s (ECCO) 28th EORTC-NCI-AACR Symposium, being held November 29 – December 2, 2016 at the Internationales Congress Center München (ICM), in Munich, Germany, brought together academics, scientists, and industry representatives from across the globe to discuss the latest innovations in drug development, target selection and the impact of new discoveries in molecular biology.

During the symposium, Richard Wooster, Ph.D., President, Research & Development and Chief Scientific Officer of Tarveda Therapeutics, Inc., discussed, as part of a workshop, the development of potent peptide-drug conjugates and the selective miniaturized-drug conjugates for the treatment of patients with solid tumors.

“Tarveda takes a novel approach to cancer therapeutics through our Pentarins™, which are potent and selective, miniaturized conjugates uniquely designed to penetrate deep into solid tumors, accumulate their payload, and cause cancer cell death,” Wooster said.

“Due to their small size and innovative design, Pentarins are created through chemistry to address the deficits of larger ADCs, which have been hindered due to slow and limited penetration in solid tumors and payload dissociation resulting in target competition and toxicities of peripheral tissues. Pentarins have shown rapid penetration deep into solid tumor tissue and sustained regressions across a range of hard-to-treat cancer models,” he added.