Model-Based Interspecies Scaling for Predicting Human Pharmacokinetics of CB 4332, a Complement Factor I Protein.

Interspecies scaling of the pharmacokinetics (PK) of CB 4332, a 150 kDa recombinant complement factor I protein, was performed using traditional and model-based approaches to inform first-in-human dose selection. Plasma concentration versus time data from four preclinical PK studies of single intravenous and subcutaneous (SC) CB 4332 dosing in mice, rats and nonhuman primates (NHPs) were modeled simultaneously using naive pooling including allometric scaling. The human-equivalent dose was calculated using the preclinical no observed adverse effect level (NOAEL) as part of the dose-by-factor approach.

Intratumoral delivery of TransCon TLR7/8 Agonist promotes sustained anti-tumor activity and local immune cell activation while minimizing systemic cytokine induction.

Background: Intratumoral (IT) delivery of toll-like receptor (TLR) agonists has shown encouraging anti-tumor benefit in preclinical and early clinical studies. However, IT delivery of TLR agonists may lead to rapid effusion from the tumor microenvironment (TME), potentially limiting the duration of local inflammation and increasing the risk of systemic adverse events.

Methods: To address these limitations, TransCon TLR7/8 Agonist-an investigational sustained-release prodrug of resiquimod that uses a TransCon linker and hydrogel technology to achieve sustained and predictable IT release of resiquimod-was developed.

Design and Preclinical Development of TransCon PTH, an Investigational Sustained-Release PTH Replacement Therapy for Hypoparathyroidism.

Hypoparathyroidism (HP) is a condition of parathyroid hormone (PTH) deficiency leading to abnormal calcium and phosphate metabolism. The mainstay of therapy consists of vitamin D and calcium supplements, as well as adjunct Natpara (PTH(1-84)). However, neither therapy optimally controls urinary calcium (uCa) or significantly reduces the incidence of hypercalcemia and hypocalcemia.

Comparative evaluation of administration methods for a vaccine protecting rainbow trout against Yersinia ruckeri O1 biotype 2 infections.

Numerous outbreaks of enteric red mouth disease (ERM) caused by Yersinia ruckeri O1 biotype 2 in rainbow trout farms are currently being recorded despite established vaccination procedures against this disease. This could indicate that the currently used application of single immersion vaccination (using a commercial vaccine AquaVac(®) RELERA™) does not provide full protection. We elucidated by a controlled duplicated experiment if different vaccine administration methods can improve level and extent of protection.

Determining vaccination frequency in farmed rainbow trout using Vibrio anguillarum O1 specific serum antibody measurements.

Background: Despite vaccination with a commercial vaccine with a documented protective effect against Vibrio anguillarum O1 disease outbreaks caused by this bacterium have been registered among rainbow trout at Danish fish farms. The present study examined specific serum antibody levels as a valid marker for assessing vaccination status in a fish population. For this purpose a highly sensitive enzyme-linked immunosorbent assay (ELISA) was developed and used to evaluate sera from farmed rainbow trout vaccinated against V.