Research and Development

Serpin Pharma has developed a family of synthetic peptides derived from naturally occurring serine protease inhibitors (Serpins) containing a unique anti-inflammatory core motif. These peptides retain the anti-inflammatory and cell-protective signaling without inhibiting the plasma serine proteases (Issued Patents #8,975,224, US 9951104 B2, and US 8975224 B2).

The peptides target LRP1, a common Serpin receptor, found to promote an anti-inflammatory and pro-survival environment. The lead peptide, SP16, consists of 17 amino acids derived by excision of a 36-39 amino-acid-long peptide fragment of alpha-1 anti-trypsin (AAT) that retains the LRP1 binding motif. SP16, along with other candidate peptides, was screened using an NFkB reporter cell line and the mouse LPS challenge model for anti-inflammatory function. SP16 was chosen as the lead peptide as it was the smallest natural peptide that maintained high potency.

SP16 was modified to improve plasma stability, bioavailability, and enhanced efficacy. PK studies determined the half-life (t1/2) of SP16 as 3.3 hours, and a receptor binding study testing 111 receptors indicated no concern for off-target interaction.

SP16 has demonstrated retention of the majority of the tested anti-inflammatory and immune-modulatory properties of AAT. We have documented the anti- inflammatory and cell-protective effects of SP16 in numerous animal models of inflammation such as rheumatoid arthritis, gouty arthritis, acute myocardial infarction (AMI), Type I and II diabetes, and endotoxemia. Serpin Pharma tested SP16 in an LPS sepsis model in vivo. SP16 treatment in a lethal endotoxemia model increased survival from 0 to 60 percent at the 72-hour study endpoint. In addition, we showed that SP16 is effective in ameliorating Graft Versus Host Disease, with subsequent sepsis exacerbated by a strong Cytokine Response Syndrome (CRS). These results suggest that SP16 is a promising new therapeutic in the very small drug arsenal available to combat sepsis, and likely works through downmodulation of CRS.

Serpin Pharma has completed GLP-toxicology and safety pharmacology preclinical studies for SP16 in acute myocardial infarction (AMI). The results of these studies show that subcutaneously administered SP16 is systemically well tolerated at doses far exceeding the planned clinical dose. The IND for SP16 treatment has been approved by the FDA to proceed with Phase I clinical trials currently conducted at Virginia Commonwealth University.