MESSAGE FROM THE PRESIDENT AND CEO

by Andrew Casey, BIOTECanada

AT THE TIME OF WRITING THE WORLD HAS REACHED THE TWOYEAR MARK OF THE COVID19 PANDEMIC. While there are clearly differing opinions of how and when our societies and economies should transition out of life with restrictions, that the debate can even be had is in large part due to this industry’s timely delivery of highly effective vaccines. At a minimum, hundreds of thousands of lives have been saved and the overall impact of the pandemic on economies has been greatly reduced as a result of the solutions this industry discovered, developed, and delivered. While there is still some COVID-19 road ahead, many governments are wisely preparing for the possibility of another pandemic at some point. Having spent over two years solving for COVID-19 on the fly, it is clear there is now a strong desire to avoid repeating the experience and prepare now for COVID-30 or whatever other global health threat may emerge down the road. Global investors are also seeing the opportunity the sector represents. For the most part, the increased recognition of the sector’s value and importance is good news for Canada. Canada’s biotech ecosystem is built on a reputation of strong scientific research including a diverse mix of early-stage companies, universities, incubators/accelerators, research centres, investors, and multinational pharmaceutical/biotech companies. From a biomanufacturing/vaccine perspective, Canada is also home to two established commercial vaccine facilities, BioVectra’s Atlantic Canada premises and the soon to be operational Medicago site in Quebec City. Combined, there is in place a valuable life sciences sector and biomanufacturing base in Canada which can form the foundation upon which to build. Investing more in enhancing this foundation will not only help meet the preparedness objective, but if done strategically, can be leveraged as the federal government moves forward with its life sciences strategy and corresponding biomanufacturing initiative. It is important to recognize that Canada is not alone in its quest to grow its life sciences sector and biomanufacturing capacity. Not surprisingly, the pandemic has focussed the attention of many governments globally on the importance of building strong domestic biotech sectors. As federal and provincial governments implement strategies to grow the sector, attract investment and talent, Canada will need to keep pace with other nations seeking to do likewise. It is a competitive space where the elbows will be sharp and high. As the COVID-19 fog begins to lift and we focus on moving forward, rebuilding and preparing for future challenges (including that of global climate change which has continued unabated throughout the pandemic, as evidenced by the UN International Panel on Climate Change report), the importance of this sector and the solutions it provides will only increase. Accordingly, the federal government is making significant investments to enhance Canada’s life sciences and biomanufacturing sector. There remains much work to be done to attract investment, grow and diversify the pool of talent and ultimately create Canadian based anchor companies. It will not be easy, but the past year represents a solid start with enormous promise for the future. The months ahead represent an important opportunity for the entire BIOTECanada membership which is representative of the Canadian biotech ecosystem.

Therapeutic Applications for Messenger RNA Lipid Nanoparticles

by Dr. Ying Tam, MSc, PhD, Chief Scientific Officer, Acuitas Therapeutics

ALTHOUGH THE THERAPEUTIC POTENTIAL OF MESSENGER RNA (MRNA) WAS FIRST PROPOSED MANY YEARS AGO, technical advances to mRNA itself (improved translatability, stability and manufacturability and reduced immunogenicity) and the enabling lipid nanoparticle (LNP) delivery systems (improved potency and safety) has only recently allowed this potential to be realized. As a result of COVID-19, mRNA has been proven, and now has widespread acceptance as an infectious disease vaccine. This opens the opportunity for mRNA LNP-based drugs that are in development to treat a broad range of diseases and represents a technology that could revolutionize the drug development process. VACCINES: The successful development of mRNA LNP vaccines was vital in the battle against COVID-19. Large clinical trials and real-world vaccination experience have shown that COMIRNATY® (Pfizer/BioNTech) and SPIKEVAX™ (Moderna) are safe and they provide robust protection against infection and illness from the SARSCoV-2 virus. With this, it is expected that infectious disease vaccines will remain a major focus of mRNA therapies. In fact, significant efforts are underway in pursuing vaccines for many infectious diseases such as influenza, tuberculosis and hepatitis C, among others. Furthermore, mRNA’s success in battling COVID-19 has reinvigorated efforts in vaccine development against particularly challenging infectious diseases with a high global health impact, such as malaria and HIV. Further, the speed at which effective and safe vaccines can be developed and manufactured on a large scale, using a scalable process consistent across multiple vaccines, demonstrates that compared to conventional vaccine approaches, mRNA LNP vaccines are uniquely positioned to address the health and societal threat of epidemic outbreaks caused by new or re-emergent pathogens such as Zika, Ebola and pandemic influenza. The ability to not only induce antibodies, but also develop potent adaptive cellular immune responses has highlighted the potential value of mRNA LNP as vaccines to induce anti-cancer immune responses to treat malignant disease. GENE EDITING: Another exciting therapeutic application for mRNA is genome editing. The identification and development of genome editing systems such as CRISPR/Cas9, zinc-finger nucleases and TALENs engineered to precisely edit cellular DNA sequences to stably correct mutated genes, and deactivate disease-causing genes has led to a renaissance in gene therapy. However, safe and efficient delivery of the editing systems to target cells in the body represents a significant challenge. This can be addressed using non-viral LNP delivery of mRNA to encode the editing enzymes. LNP delivery is able to accommodate the larger payloads required for editing systems compared to alternative approaches. LNP delivery may also provide potential safety benefits, including avoiding direct risks associated with viral delivery systems and prolonged enzyme expression to minimize the likelihood of editing at non-target sites. IN VIVO PROTEIN PRODUCTION: Perhaps the most direct application of mRNA LNP as a therapeutic is for in vivo production of therapeutic proteins. In one aspect, mRNA LNP could be used to produce an intracellular or secreted protein to treat diseases where gene mutations have resulted in either loss of protein expression or production of a non-functional protein. This could be applied to a range of inherited monogenic diseases including hemophilia and lysosomal storage diseases, such as Fabry and Gaucher disease. In addition to protein replacement, mRNA LNP could be used to deliver therapeutic proteins such as growth factors to treat diseases. These range from erythropoietin for anemia, hepatocyte growth factors to treat chronic and acute liver diseases, and immunomodulatory chemokines and cytokines for immunotherapy of cancer. Finally, mRNA LNP have been applied as a form of passive immunization, mediating in vivo production of monoclonal antibodies to provide protection against infectious pathogens and anti-cancer therapies. mRNA therapeutics represent a rapidly expanding drug class. With the first mRNA-based drugs having been approved and a range of others in development, the breadth of applications and the number of diseases that mRNA drugs will ultimately be used to treat is difficult to estimate. With advances that have been made over the past decade, the validated safety and efficacy, and global acceptance, it is clear that mRNA therapeutics have the potential to treat a broad range of serious human diseases – helping to advance human health in multiple areas of focus that have been recently out of reach.