Interfacing Chemical Biology and Drug Discovery

RICT 2021

56th International Conference on Medicinal Chemistry
56èmes Rencontres Internationales de Chimie Thérapeutique

 Virtual Event    July 7-9, 2021

2021 Editorial - written by Dr Romain Gosmini, Galapagos

Coronavirus disease 2019 (COVID-19) pandemic dominated in 2020. Beyond the terrible impact on human population and on the global economy it totally modified our social life, the way we work, meet and exchange. More specifically RICT 2020 conferences were cancelled. We all had to cope with new living conditions. To apply social distancing and maintain interactions video conferences proved to be efficient if not warm. These RICT 2021 conferences will take place exclusively virtually.  Some of us will miss the stimulating atmosphere of the conferences, meeting friends and colleagues, chatting and sharing ideas with passion.

Hopefully it will also be the last one to be held only virtually.  The huge efforts developed to try as fast as possible to identify medicines to limit the spread of COVID-19 have succeeded. Vaccination gave the promptest positive signals of a possible light at the end of the tunnel. The Small Molecule approach, which showed its efficacy in the past by offering the only treatment for AIDS patients and a cure for hepatite C infected patients, did not achieve yet significant results. Timelines for small molecule discovery are long. Some teams are pursuing intense efforts in the field anticipating that new coronavirus will pass to humans and that Small Molecules treatments could deliver a precious therapeutic alternative. The paramount success of vaccination was in good part due to the new mRNA vaccines. Media covered intensively the new mRNA approach and detailed the nice success stories about Moderna, BioNTech and the pioneer mindset of their founders. Less emphasis was given to the essential work done in parallel, which took more than 30 years to optimize the lipid nanoparticles without which mRNA would be unstable and unable to enter the cells. The critical progress done on the lipid nanoparticles field and the tremendous added value that can be achieved illustrate the importance that specific drug delivery can take on. Likewise, the recent identification of an orally available PCSK9 antisense oligonucleotide targeting the liver, enabled by N-acetylgalactosamine conjugation, is an additional example of the key contribution and the broad spectrum of applications that specific drug delivery will bring in the future. This topic will be addressed during this RICT meeting with a dedicated theme Tackling New Challenges in Delivery Systems and Drug Formulation.

The aim for a sustained pace of new therapeutics delivery to treat unmet medical need and bring benefit to patients puts high pressure on research organisations and compels Drug Discovery (DD) to constant evolution. Adaptation of DD took regularly place with the implementation of various new paradigms in response to specific challenges. New metrics and druggability guidelines, focusing attention on improved absorption, solubility and limited lipophilicity emerged in 2005 to tackle the declining number of new chemical entities entering the market. More recently, to expand the drying up pool of biological targets New Modalities were intensively developed as an alternative to the classical modulation of a protein function by a small molecule. Over the past decades, the rise of the target-centric approach in Drug Discovery was made possible with the innovative development of critical chemical tools to bring new molecular-level insights into the mechanisms underpinning biological processes. The phenotypic approach also is dependent on innovative Chemical Biology for the generation of chemical probes to identify the biological target and further understand the underlying mechanism of action. This year, once again, to stress their remarkable interdependency, the title of these 2021 RICT meeting will be Interfacing Chemical biology and Drug Discovery and the Conferences will start with the session on Chemistry in Living Systems & Chemical Biology for Targets Identification.

The rise of new modalities supported by the chemical biology progress has increased the opportunities to tackle Protein-Protein, Protein-DNA/RNA interactions and Protein degradation. From the first demonstration of their potential biological interest, by injection in cell to palliate their absence of cell permeability, to their current evaluation as oral drug therapies in phase 2 clinical studies, the bifunctional degraders molecules recruiting an E3 ligase to mediate the ubiquitination of the targeted protein have reached an outstanding milestone. These impressive progresses have been accompanied with many questions raising as for example the extension of their application to non-cancer diseases, the use of ligands with moderate binding affinities, the E3 ligase tissue expression and protein half-life limitations and their safety. The session Drugging the Undruggable and New Modalities in Drug Discovery will help better understand the progress and the challenges of these new modalities.

The recent controversial approval by US regulators of aducanumab as the first treatment to target a likely cause of Alzheimer’s disease is triggering many varied reactions in the scientific community. Expectations are high and therapeutic progress difficult within this extremely complex disease area. With a likelihood of approval (5.3%) from Phase I over 2011-2020 slightly below Neurology, Oncology is also a particularly challenging disease and the focus of the largest number of clinical trials. The combined progress on new drug modalities such as ADCs and CAR-T cells therapies, Immuno-Oncology and the identification of biomarkers that help better stratify patients are contributing to improve the success rate and bring hope for the patients. Several presentations spread over different sessions will give a nice opportunity to catch up with recent progress on these two themes Innovations in Cancer Therapeutics and Recent Trends in Drug Development for Neurodegenerative Diseases.

The evolution of DD is well reflected by the way new Drugs are discovered. The session Case Studies: Moving New Chemical Entities to the Market will allow to learn detailed information on the identification of drugs. An interesting example of the growing place that new paradigms, such as protein degradation, are taking today will be illustrated with the Selective Estrogen Receptor Degrader case.

COVID-19 has touched our lives to different degrees, but we have all learned from it. Huge scientific mobilization can achieve seemingly insurmountable challenges. Hope and risk were 2 pillars of this success. Hope to find a way out of this crisis and the essential risk to be taken with innovative scientific approaches, investments and logistics anticipation without any certainty. As scientists we are used to live with these two drivers. The future scientific successes will be based on our ability to pursue risky activities and keep hope to bring benefit to patients. Hope is a risk that must be run (l’espérance est un risque à courir, Georges Bernanos). I hope these RICT2021 will strengthen our knowledge and motivations to still push a little bit further the frontiers of chemical biology and Drug discovery.

Romain Gosmini


Romain Gosmini (Galapagos, Director medicinal Chemistry, France)
Dr Romain Gosmini is Director of Medicinal Chemistry at Galapagos, Romainville, France. In 1991 he did his PhD in organic synthesis under the guidance of Prof. Jean Normant at the University Paris VI. He completed a postdoctoral fellowship in Geneva with Prof. Peter Kundig. In 1994 he joined Glaxo where he worked as medicinal chemist and led the chemistry of several programs until 2009. Just after he started working at Galapagos as Group Leader. He is Interested in the different phases of DD (HF, H2L, LO until PCC identification) and involved in various projects such as kinases, proteases, GPCRs and phenotypic, new modalities and degraders, DEL Technology, tissue delivery, Photo-probes, chemical biology. He worked in various disease areas such as cardiovascular, metabolic, inflammation, fibrosis, infectious disease, Cystic Fibrosis, osteoarthritis…