With Covid-19 taking so much of the drug discovery and development’s focus over the last two years, it has been easy to overlook other areas within the sector that deserve our attention. With Q1 on its way out, Lu Rahman highlights the technology that will play a valuable role for the rest of the year.
Thanks to Pfizer BioNTech and the Comirnaty Covid-19 vaccine, followed by the Moderna Spikevax product, messenger RNA (mRNA) technology recently came into the spotlight. While the technology itself has been on our radar for some time, it has experienced something of a new lease of life and has the potential to transform a range of diseases from HIV to cancer. One example is the trial recently announced by IAVI and Moderna for HIV vaccine antigens delivered through mRNA technology. Mark Feinberg, President and CEO of IAVI, said: “The search for an HIV vaccine has been long and challenging, and having new tools in terms of immunogens and platforms could be the key to making rapid progress toward an urgently needed, effective HIV vaccine.”
Dr. Tom Knapman, Directorof Strategic Brand at SCIEX, described the relevance of mRNA in a recent DDW article: “We are in a new era for mRNA as we look to upgrading our immune systems regularly, called ‘forever boosting’ to fend against potential viral infections. At the same time,there is increasing research on mRNA’s applicability to treat non-communicable diseases, like cancer. This trend for greater application of mRNA therapeutics, and more generally in the research and development of precision and personalised therapies like genomic medicines, means that we need more powerful analytical tools. It’s no longer enough to know what a compound is and what it’s comprised of. Now, scientists often need to also know exactly how that compound works inhuman biology.”
Dr Pirkko Muhonen, Senior Field Application Scientist of Nucleic Acid Therapeutics at Thermo Fisher Scientific, also shared what’s next for RNA-based medicine post-pandemic with DDW. She highlighted the development of self-amplifying RNA vaccines to combat infectious diseases and cancer. “Another area of RNA research that’s garnering enthusiasm with vaccine developers is self-amplifyingRNA (saRNA). Like mRNA, saRNA is a single-stranded and linear RNA molecule that enters the cytoplasm to generate an antigen of interest and promote an immune response.1 When compared to current mRNA vaccines, self-amplifyingRNA molecules contain an additional sequence element to encode for an enzyme that can amplify the replication of the mRNA for extended periods of time. This allows the mRNAto remain active in target cellsand produce more proteins fora longer time.” She adds that like mRNA, saRNA vaccine formulations can also be made with promisingly simple manufacturing workflows.1 “This versatile RNA platform technology is being considered for treatment of infectious disease as well as certain types of cancer, including melanoma and colon carcinoma.”
The role of technology
Where to start with this one? Lab technology has always been key to the drug discovery sector but in recent years we have seen its relevance accelerate. As the sector explores ways to get to market faster and more efficiently, we are witnessing an increased use of automation, robotics and integrated digital technology as their benefits become apparent to the drug discovery and development community.
The Covid-19 pandemic served as something of a catalyst for innovation as many businesses examined ways to optimise processes and workflows and to avoid bottlenecks or downtime caused by lockdowns or social distancing in the workplace. Technology is a broad term and choosing exciting innovation depends on many factors – application and budget being just two considerations. We tend to immediately head to AI when we talk about technology in the lab. Of course, there is much that AI can offer the drug discovery process – its use within the process is continually on the rise – and we also have what is being hailed as a potential ‘revolution’ for the sector; digital twins. This is a growing and exciting area to be part of and rightly so, but these are just two examples among many. Effective technology doesn’t have to be high-end or budget-busting. There are ways that innovations can be used to improve the way novel molecules are identified, to boost drug screening or chemical synthesis for example. According to Daniel Rines, Senior Director at Strateos: “Our industry must re-imagine laboratories as intelligent and automated data centres to generate clean and reproducible data rapidly and at low cost to support the next wave of life-changing therapeutics.” Rines believes that “the lab of the future is now”. Automated drug discovery can be done from the comfort of a coffee shop. “The capital investments typically required for pharmaceutical research and development are gone. The pandemic has accelerated this notion, reshaped our landscape, and erased the preconception that science must be done by humans in the lab. We are seeing these trends materialise in real time and drive an exponential increase in demand for hight hroughput experimentation; further exploration of new reagent space like mRNAs, exotic and rare antibodies, CAR-T and other macromolecules to find better therapeutics; and also forming tighter partnerships between academia and industry, ultimately leading to more novel discovery projects all while embracing the shift to the cloud.”
Another effect of the pandemic has been felt within the clinical research space. Decentralised clinical trials (DCTs) are discussed often at the moment – the use of technology means that patients no longer need to be tied to a specific location.The Association of Clinical Research Organizations (ACRO) released its DCT Toolkit last year which lays out a vision for how DCTs can be planned and executed now and in the future.The organisation recognises that when Covid-19 hit in March 2020, clinical trial participants were cut off from in-person clinical research visits. CROs and technology companies were often able to keep active clinical trials up and running by using remote technologies –telemedicine, remote sensors, wearable devices. This allowed patients to continue to get the clinical care and medical evaluation that are part of a clinical trial. Temitope Keyes, Executive Director of Business Development at encapsia, recently told DDW: “Clinical trials are now more complex than ever, and sites and patients can (and will) be anywhere. Data is cascading in from a variety of sources and, when coupled with expanded trial data volume, has a continuous growing impact on study timelines and inefficiencies.”
However, she also points out: “A quick glance at today’s clinical trial operations makes it clear that, in reality, technology has not kept pace with the advance of today’s decentralised, digital world. There has been a crucial shift towards the implementation of digitalisation across the continuum of trial conduct, especially in the adoption of new patient- and site-centric technologies, and tools that deliver data immediately along with improved processes that provide for continuing patient safety.”
Keyes offers some expert advice on how this area needs to make progress: “DCTs come in so many different variations, it’s important for sponsors to shift from a place where they’re trying to mould their trials to fit the tools they have, to one where they actively choose the right tools that fit their trials from the get-go.The technology used before the pandemic is no longer good enough and the industry must embrace fit-for-purpose technologies built to enable today’s trials. “To do data differently, change must be embraced, using partners who can provide that revolutionary technology as well as technical consultancy, expertise to support that shared vision.”
Volume 23, Issue 2 – Spring 2022
1: Bloom K, van den Berg F, ArbuthnotP. Self-amplifying RNA vaccinesfor infectious diseases. Gene Ther.2021;28(3-4):117-129. doi:10.1038/s41434-020-00204-y.