Saurabh Aggarwal

What's fueling the biotech engine?

A survey of market trends for biotech products shows that only a handful out of more than one hundred biologics have been fueling the double-digit rise in revenues in the sector.

Targeting the cancer stroma with a fibroblast activation protein-activated promelittin protoxin.

Fibroblast-Activation Protein-α (FAP) is a membrane-bound serine protease that is expressed on the surface of reactive stromal fibroblasts present within the majority of human epithelial tumors but is not expressed by normal tissues. FAP is a postprolyl peptidase that differs from other dipeptidyl prolyl peptidases such as diprolylpeptidase 4 in that it also has gelatinase and collagenase endopeptidase activity. Therefore, FAP represents a potential pan-tumor target whose enzymatic activity can be exploited for the intratumoral activation of prodrugs and protoxins. To evaluate FAP as a tumor-specific target, putative FAP-selective peptide protoxins were constructed through modification of the prodomain of melittin, a 26 amino acid amphipathic cytolytic peptide that is the main toxic component in the venom of the common European honeybee Apis milefera. Melittin is synthesized as promelittin, containing a 22 amino acid NH2-terminal prodomain rich in the amino acids proline and alanine. In this study, peptides containing truncated melittin prodomain sequences were tested on erythrocytes to determine the optimal prodomain length for inhibiting cytolytic activity. Once optimized, modified promelittin peptides were generated in which previously identified FAP substrate sequences were introduced into the prodomain. Peptide protoxins were identified that were efficiently activated by FAP and selectively toxic to FAP-expressing cell lines with an IC50 value in the low micromolar range that is similar to melittin. Intratumoral injection of an FAP-activated protoxin produced significant lysis and growth inhibition of human breast and prostate cancer xenografts with minimal toxicity to the host animal. [Mol Cancer Ther 2009;8(5):1378–86]

What's fueling the biotech engine—2007

Despite losses in revenue from erythropoietins, historically the highest earner of all biologics, more than 100 biotech drugs continued their upward trend in sales begun in 2006, with antibodies and insulin analogs fueling growth at double-digit rates.

A dimeric peptide that binds selectively to prostate-specific membrane antigen and inhibits its enzymatic activity

Prostate-specific membrane antigen (PSMA) is highly expressed by both normal and malignant prostate epithelial cells and by the neovasculature of many tumor types; however, it is not expressed by normal endothelial cells or other normal tissues. PSMA, therefore, represents an attractive candidate for selectively targeted therapies for prostate and/or other solid tumors. As an alternative approach to antibody-based anti-PSMA therapies, small peptides that bind selectively to PSMA-producing cells can be used to deliver cytotoxic drugs, protein toxins, and viruses selectively to malignant sites while minimizing systemic toxicity to normal tissues. Small peptides are relatively inexpensive to produce, not immunogenic, and easily coupled to cytotoxic agents. In the present study, a random phage library consisting of linear 12 amino acid peptides was used to identify peptides that bound selectively to PSMA. From a series of monomeric peptides, one with the sequence WQPDTAHHWATL was used to show binding of soluble peptide to PSMA. A dimeric version of this peptide showed markedly enhanced binding to soluble PSMA and an IC50 of 2.2 micromol/L for inhibition of PSMA enzymatic activity. Fluorescently labeled dimeric peptide bound selectively to PSMA-producing prostate cancer cells in vitro with no significant binding to non-PSMA-producing cells. Molecular modeling of the dimeric peptide revealed that histidine residues in close vicinity can efficiently coordinate a divalent ion and hold the peptide in a favorable configuration for binding and subsequent inhibition. These dimeric peptides, therefore, represent putative PSMA-selective targeting agents that are currently being evaluated for selective binding in vivo.

What's fueling the biotech engine—2010 to 2011

In the past year, biologics sector sales grew by single digits, driven by monoclonal antibodies and insulin products. New product launches are showing mixed results and are facing rising challenges from changes to reimbursement policies.

What's fueling the biotech engine—2009–2010

Last year, the biologics sector managed single-digit growth in the United States, driven mainly by products indicated for oncology, diabetes and autoimmune disorders. Lurking on the horizon, though, are challenges, such as pricing, competition and follow-on molecules.

What's fueling the biotech engine[mdash]2009-2010

Last year, the biologics sector managed single-digit growth in the United States, driven mainly by products indicated for oncology, diabetes and autoimmune disorders. Lurking on the horizon, though, are challenges, such as pricing, competition and follow-on molecules.

What's fueling the biotech engine[mdash]2011 to 2012

Sales in the biologics sector show modest but healthy growth rates for the fourth consecutive year, with cancer drugs garnering the greatest revenues. As the diabetes epidemic grows and innovation of insulins continues, drug companies in that space are moving up in the ranks.

What's fueling the biotech engine—2011 to 2012

Sales in the biologics sector show modest but healthy growth rates for the fourth consecutive year, with cancer drugs garnering the greatest revenues. As the diabetes epidemic grows and innovation of insulins continues, drug companies in that space are moving up in the ranks.

A survey of breakthrough therapy designations.

As of last month, 41 products have been granted breakthrough therapy designations by the US Food and Drug Administration—drugs against cancer, hepatitis C and monogenetic diseases predominate.