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Top 10 Drug Discovery Trends to Watch in 2019

Jan 09, 2019

Last year was a busy one for the pharmaceutical and biotechnology industry—the Food and Drug Administration (FDA) approved an all-time high of 59 new molecular entities. In order to keep that pace in 2019, the FDA streamlining processes and updating regulations. But how will drug discovery help drive forward innovations in the coming year?

Below, researchers from across disciplines at Charles River discuss which trends they expect will propel the development of novel therapeutics forward this year.

Utilizing GPU computing and physics-based algorithms in CADD - David Clark, PhD, Research Leader, CADD

The holy grail of computer-aided drug design (CADD) is the accurate prediction of the binding affinity of a drug molecule for its protein target. If this were possible—even the prediction of relative, rather than absolute, binding affinities—the impact on drug design would be phenomenal as it would enable scientists to zero in rapidly on the key compounds to make, and to discard, poor candidates without having to synthesize them. In recent years, some progress towards this goal has been made as massive computing resources based on high-end graphics cards (usually used in computer gaming) have been applied to simulations of protein-ligand complexes, allowing better estimates of binding affinities … but only in some cases. Anecdotally, the technology has been shown to work in some cases, but not all—and it’s not possible to tell beforehand which is which. But it’s still relatively early days and the hope is that with growing experience and continuing development of the underlying methodologies, the success rate of this technique will improve.

The development of PDX platforms for childhood cancer for oncology research - Julia Schueler, PhD, Research Director, Oncology

Cancer remains the leading cause of disease-related death in children. In most of the cases curative treatment options are rare. Preclinical drug testing to identify promising treatment options that match the molecular make-up of the tumor is hampered by the lack of available models. PPPs (public-private partnerships) in Europe, as well as in the U.S., were built in the last few months to close this gap of models and create robust and reliable platforms for drug development of childhood cancer. The possibility of having a PDX based platform validated by distinct molecular characterization of high-risk pediatric malignancies in combination with thorough standard of care data will significantly accelerate the development of more precise and efficacious drugs.

Using flow cytometry to learn how immunotherapies fight cancer - Christoph Eberle, MICR, PhD, Principal Scientist, Oncology

Since the first instruments using fluorescence-based detection came to market, flow cytometry technology has been widely utilized. As we learn more about the immune system’s role in incurable diseases, flow cytometry is suddenly popular again, including in the area of Phenotyping of tumor-infiltrating lymphocytes (TIL) by flow cytometry is a common readout from animal models used in oncology. Experimental studies assess whether and how immune cells within this disguising microenvironment may change under various dosing regimens. Measurable changes in their frequency, composition, distribution, and function may help determine a possible therapeutic outcome. Ultimately, the same information can be of prognostic and predictive value along the drug development journey.   

Harnessing intrathecal drug delivery to circumvent the BBB - Ria Falvo, Principal Research Scientist, Toxicology Reporting

The continued increase in demand for treatment of central nervous system (CNS) diseases and the bypass of the blood-brain barrier with intrathecal drug administration is a hot topic right now. Beyond the last century, the blood-brain barrier (BBB) was conceived to be a passive, impermeable barrier that shielded the brain from the blood’s trajectories. However, revolutionary work over the years has given way to the idea that the BBB is an active, selectively permeable channel for transport between the blood and the brain of proteins, cells, and substrates that have access to transport systems localized within the BBB membranes. With these innovations in motion, intrathecal delivery, which allows you to deliver the drug to the central nervous system by circumventing the BBB, offers some unique opportunities for developers of CNS drugs. It allows you, among other things, to administer genetically-engineered vectors into the central nervous system to express targeted proteins or oligonucleotides that modulate the expression of genes in order to address unmet medical needs for neurodegenerative and often rare diseases. This potentially overcomes challenges with intravenous administration that are not always able to deliver sufficient therapeutic levels across the BBB. Prospects for the intrathecal delivery are on the rise with the increasing need to treat patients and genetic diseases, including orphan diseases affecting pediatric and juvenile populations.  

Immunophenotyping in studying CNS diseases - Tuulia Huhtala, PhD, Head of Biomarkers and Molecular Imaging, CNS Discovery

Flow cytometric technology has been around for 50 years. As we learn more about the immune system’s role in incurable diseases, the tool is , particularly in the study of CNS diseases, like Alzheimer’s or Parkinson’s. As immunophenotyping may reveal not only inflammatory processes, but also the activation status of immune cell subsets, it can guide selecting individual immunomodulatory therapies. In CNS animal models this provides insight in the dynamics of peripheral and resident cells. Understanding the innate and adaptive immune cell status within the CNS and in the periphery during disease progression can be applied to monitor biomarker expression profiles as well possible pharmacodynamic changes related to treatment.

The development of phage therapies to combat drug-resistant infections - Rana Samadfam, PhD, DABT, MSc, Scientific Director, In Vivo Pharmacology

With multi-drug resistant infections escalating, phage therapy might help us get back in the fight and beat the superbugs at their own game. The arrival of antibiotics in the 1950s heralded what many thought would be the death of dangerous infections. Unfortunately, antibiotic resistance genes, now abundant in the environment and encouraged by the overuse and misuse of antibiotics, have diminished the effectiveness of these infection fighters. In the age of multi-drug resistance, could phage therapy be the effective alternative to antibiotics we have been searching for? Phage therapy relies on the use of naturally-occurring phages to infect and lyse bacteria at the site of infection. Although there are several clinical trials ongoing, there is only one FDA-approved phage therapy product on the market that is being used to kill a virulent food-borne pathogen. But with tools like CRISPR-Cas9, we now have a way of understanding phages and their bacterial hosts, which could open the door to using phages for selective diseases. Let’s beat the superbugs at their own game!

A new class of naturally-occurring antibiotics - Charlotte Cumper, Infection Laboratory Scientist, Early Discovery

With the failure of conventional antibiotic treatment becoming a global crisis, research is looking increasingly to novel approaches—for example, bacteriophage therapy or combining existing antibiotics with drugs that inactivate resistance mechanisms. Earlier this year a new class of antibiotic was announced: odilorhabdins (ODLs) are produced by symbiotic bacteria found in nematode worms and target the bacterial ribosome. These have been shown to be effective against carbapenem-resistant Enterobacteriacae. Another up-and-coming area is host-directed therapy, which involves modulating various host factors, such as boosting the immune system or targeting pathways that may contribute to immunopathology. This area is showing particular promise in the treatment of drug-resistant TB (the world’s leading infectious killer). Research in this field looks set to continue expanding.



David Clark, PhD, Research Leader, CADD; Julia Schueler, PhD, Research Director, Oncology; Christoph Eberle, MICR, PhD, Principal Scientist, Oncology; Ria Falvo, Principal Research Scientist, Toxicology Reporting; Tuulia Huhtala, PhD, Head of Biomarkers and Molecular Imaging, CNS Discovery; Rana Samadfam, PhD, DABT, MSc, Scientific Director, In Vivo Pharmacology; and Charlotte Cumper, Infection Laboratory Scientist, Early Discovery; all with Charles River.


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