Search results for "Drug Development"
showing 10 items of 115 documents
Abstract CT020: MERIT: introducing individualized cancer vaccines for the treatment of TNBC - a phase I trial
2016
Abstract The majority of metastatic cancers remain incurable since the current methods of treatment often fail to target the heterogeneous nature of each individual patient's tumor. Personalized approaches targeting each individual patient's tumor may therefore bring significant improvements. The Mutanome Engineered RNA Immuno-Therapy (MERIT) consortium will clinically validate a pioneering RNA-based immunotherapy concept for the treatment of triple negative breast cancer (TNBC) by targeting shared tumor antigens and individual neo-antigens in TNBC patients. MERIT combines two personalized treatment concepts: (i) treatment with vaccines containing “off-the-shelf” mRNAs selected from a pre-s…
LC-MS untargeted metabolomic analysis of drug-induced hepatotoxicity in HepG2 cells
2015
Hepatotoxicity is the number one cause for agencies not approving and withdrawing drugs for the market. Drug-induced human hepatotoxicity frequently goes undetected in preclinical safety evaluations using animal models. Human-derived in vitro models represent a common alternative to in vivo tests to detect toxic effects during preclinical testing. Most current in vitro toxicity assays rely on the measurement of nonspecific or low sensitive endpoints, which result in poor concordance with human liver toxicity. Therefore, making more accurate predictions of the potential hepatotoxicity of new drugs remains a challenge. Metabolomics, whose aim is to globally assess all the metabolites present …
A real options game of alliance timing decisions in biopharmaceutical research and development
2017
Abstract In this article we examine the alliance timing trade-off facing both pharmaceutical and biotech firms in a stochastic and competitive environment. Specifically, we introduce a real options game (ROG), where a pharmaceutical company can choose between two competing biotech firms by sequentially offering a licensing deal early or late in the new drug development process. We find that, when the alliance raises the drug market value significantly, the agreement is signed late in the drug development process. This suggests that the postponement effect implied by the use of real options prevails over the biotech firms’ competition effect, which would instead play in favor of an early agr…
The nonalcoholic steatohepatitis (NASH) drug development graveyard: established hurdles and planning for future success
2020
Contains fulltext : 229341.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Numerous pharmacological compounds that target the different molecular targets involved in the pathobiology of nonalcoholic steatohepatitis (NASH) are currently in clinical testing. So far, there are no regulatory approvals. AREAS COVERED: This paper sheds light on the molecular pathways involved in NASH and the drugs targeting these pathways. We have identified 10 compounds whose clinical development program has been halted. Moreover, we explore early phase clinical trials and dissect the reasons for termination of development. EXPERT OPINION: The main goal of NASH pharmacotherapy is to halt or reverse hepati…
Evolving therapies for liver fibrosis
2013
Fibrosis is an intrinsic response to chronic injury, maintaining organ integrity when extensive necrosis or apoptosis occurs. With protracted damage, fibrosis can progress toward excessive scarring and organ failure, as in liver cirrhosis. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development, with enormous potential but also high risks. Preclinical research has yielded numerous targets for antifibrotic agents, some of which have entered early-phase clinical studies, but progress has been hampered due to the relative lack of sensitive and specific biomarkers to measure fibrosis progression or reversal. Here we focus on antifibrotic approaches for li…
Competency of different cell models to predict human hepatotoxic drugs.
2014
The liver is the most important target for drug-induced toxicity. This vulnerability results from functional liver features and its role in the metabolic elimination of most drugs. Drug-induced liver injury is a significant leading cause of acute, chronic liver disease and an important safety issue when developing new drugs.This review describes the advantages and limitations of hepatic cell-based models for early safety risk assessment during drug development. These models include hepatocytes cultured as monolayer, collagen-sandwich; emerging complex 3D configuration; liver-derived cell lines; stem cell-derived hepatocytes.In vitro toxicity assays performed in hepatocytes or hepatoma cell …
Therapeutic vaccines for cancer: an overview of clinical trials
2014
The therapeutic potential of host-specific and tumour-specific immune responses is well recognized and, after many years, active immunotherapies directed at inducing or augmenting these responses are entering clinical practice. Antitumour immunization is a complex, multi-component task, and the optimal combinations of antigens, adjuvants, delivery vehicles and routes of administration are not yet identified. Active immunotherapy must also address the immunosuppressive and tolerogenic mechanisms deployed by tumours. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications …
A Model‐Based Workflow to Benchmark the Clinical Cholestasis Risk of Drugs
2021
We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes in expression levels of genes involved in the enterohepatic circulation of bile acids were obtained from an in vitro assay mimicking 14 days of repeated drug administration for 10 marketed drugs. These changes in gene expression over time were contextualized in a physiology-based bile acid model of glycochenodeoxycholic acid. The simulated drug-induced response in bile acid concentrations was then scaled with the applied drug doses to calculate the cholestatic potential for each compound. A ranking of the cholest…
Recent advances and potential applications of modulated differential scanning calorimetry (mDSC) in drug development.
2016
Differential scanning calorimetry (DSC) is frequently the thermal analysis technique of choice within preformulation and formulation sciences because of its ability to provide detailed information about both the physical and energetic properties of a substance and/or formulation. However, conventional DSC has shortcomings with respect to weak transitions and overlapping events, which could be solved by the use of the more sophisticated modulated DSC (mDSC). mDSC has multiple potential applications within the pharmaceutical field and the present review provides an up-to-date overview of these applications. It is aimed to serve as a broad introduction to newcomers, and also as a valuable refe…
Antitumoral compounds from vertebrate sister group: A review of Mediterranean ascidians
2020
Among the diseases that afflict the human population, cancer is one for which many drug treatments are not yet known or effective. Moreover, the pharmacological treatments used often create serious side effects in sick patients and for this reason, it is essential to find effective and less harmful treatments. To date, marine biodiversity is a real source of metabolites with antitumoral activity and among invertebrates' ascidians have been the main source to obtain them. Mediterranean area is the richest in biodiversity and contains several ascidian species used in drugs development during the years. However, many more Mediterranean ascidian species have not been studied and could be a sour…