Entera Bio has revealed positive pharmacokinetic results from its collaborative research combining a proprietary long acting GLP-2 agonist developed by OPKO Health, with Entera’s proprietary N-Tab technology. The programme is focused on developing the first and only GLP-2 peptide tablet alternative for patients suffering from short bowel syndrome (SBS) and additional disorders involving mucosal inflammation and nutrient malabsorption.
Currently, the only approved GLP-2 agonist, which is marketed under the name Gattex (teduglutide), requires daily sub-cutaneous injections. Zealand Pharma and Ironwood are developing long acting GLP-2 therapies requiring once and twice weekly injections.
SBS is a rare and potentially life-threatening malabsorptive condition caused by a significant loss of functional bowel mass (secondary to congenital defects or disease-associated loss of absorption) or physical bowel mass (secondary to extensive intestinal resection). SBS patients have a reduced ability to absorb nutrients and fluids and are at risk of malnutrition, unintended weight loss and additional symptoms due to the loss of essential vitamins and minerals. SBS is the most common cause of chronic intestinal failure, accounting for approximately 75% of cases of chronic intestinal failure in adults and 50% such events in children.
Entera and OPKO completed a proof of concept (PoC) single dose pharmacokinetic study in rodents as the first validation for oral administration of the GLP-2 treatment. Oral tablets (1.8mg; n=15) and IV injections (2mg/kg; n=6) were administered to rats. Pharmacokinetic blood samples were taken for 24 hours post-dose and drug concentrations were analysed by a validated LC-MS/MS method.
The study’s objectives were met with oral GLP-2 tablets exhibiting significant systemic exposure. Furthermore, plasma levels achieved with the oral tablet form of the GLP-2 analogue were about ten-fold higher than therapeutic plasma concentrations reported for subcutaneously administered teduglutide (Gattex label). The pharmacokinetic analysis of the data obtained following the IV injections of the GLP-2 peptide showed the plasma half-life in rats to be about six times longer than the half-life reported for teduglutide in the same animal model (Figure 1). This data is consistent with previously reported PK data relating to OPKO’s GLP-2 peptide’s long acting profile, which had initially been developed as a weekly subcutaneous injection.
“Given the challenging compliance rates attributed to injectable GLP-2 therapy, we believe a daily tablet format may address a significant unmet need in treating SBS patients more effectively. We are pleased with this first validation for the oral GLP-2 peptide programme that we initiated in late 2023 in our collaboration with OPKO,” explained said Miranda Toledano, Entera Chief Executive Officer. “The current PK data reinforces the data we previously published combining our N-Tab technology with teduglutide in tablet form1. Based on the promising results from the current PK study, we are planning to advance the programme to assess pharmacologic effects in vivo. We look forward to updating on these data later in 2024.”