About PB01

PB01: A Unique Form of Follistatin

PB01 is recombinant human follistatin-288, the most potent form of follistatin. It is a novel biological molecule with strong anti-inflammatory and anti-fibrotic actions. PB01 binds to and neutralises the activity of the TGFß superfamily of growth and differentiation cytokines, most notably the activin family, thereby inhibiting the production of proinflammatory cytokines.

Paranta is developing PB01 for therapeutic use in the treatment of cystic fibrosis (CF) lung disease and non-small cell lung cancer (NSCLC) adenocarcinomas.

Product Pipeline

PB01 rhFS288 Primary Research Programs-01

About Follistatin

The follistatin gene is found on the long arm of human chromosome 5 (5q11.2). It is a highly conserved molecule with 98% identity between human follistatin and mouse follistatin, indicating its fundamental importance in biology.

The follistatin gene consists of six exons (from which mature proteins are built), resulting in a protein that has the following elements as shown diagrammatically below:

Paranta Biosciences' Technology

FIGURE 1 The basic structure of follistatin consists of an ‘N-terminal’ domain (ND), followed by three follistatin domains (FSD1, FSD2 and FSD3). Through alternative splicing of Exon 6, the two major forms of follistatin are follistatin 288 and follistatin 315, the latter containing Exon 6. A heparin binding sequence (HBS) is located within FSD1.
Each follistatin molecule has three similar domains, known as follistatin domains (FSD), varying individually at the amino acid level but having the same structural features. The two major forms of follistatins are FS315 and FS288.
Follistatin’s primary function results from its ability to bind and block the effects of activins.  Activins are key members of the transforming growth factor beta (TGFß) superfamily of growth and differentiation cytokines.
When a molecule of follistatin meets a molecule of activin, this results in an almost irreversible binding event that prevents activin from binding to its specific receptors and causing gene activation. The activin molecule is a dimer comprising two identical or similar ß subunits. Two molecules of follistatin are required to fully neutralize an activin molecule, as shown in the schematic below:

Paranta Biosciences' Technology

FIGURE 2 Free activin molecules are able to bind to their cellular receptors and initiate cell events such as inflammation and fibrosis. In the neutralization pathway, two molecules of follistatin bind to activin with high affinity and prevent activin from binding to its receptors.
In addition to activin, follistatin also binds with lower affinity to other members of the TGFß superfamily, including bone morphogenetic proteins (BMP’s) 2, 4, 5, 6, 7, 11 and 15 and myostatin growth development factors GDF8 and GDF9. Follistatin does not bind to TGFß1 or TGFß2, but can bind to TGFß3.
Follistatin is a glycoprotein. This glycoslyated nature of follistatin affords increased stability and circulating half-life of follistatin in vivo.  In addition, follistatin contains a heparin binding sequence (HBS) that enables follistatin to bind to proteoglycans on cell surfaces and in the extracellular matrix.

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