Dr Sophia Ononye-Onyia explains why a combination of both repurposed drugs and emerging technologies like 3D bioprinting and artificial intelligence will be crucial in beating COVID-19.
Much has already been said about the hundreds of vaccines that are currently in development for providing global protection against COVID-19 by leading research institutions and biopharmaceutical companies such as Oxford University-AstraZeneca, Inovio and Pfizer-BioNTech. However, there are mixed opinions on the efficacy and safety of these vaccines particularly with regard to long-term survival. Additionally, the use of anti-malarial drugs for managing the coronavirus remains somewhat controversial based on fairly limited scientific data. Taken together, our post-COVID-19 survival hinges on a delicate balance between the use of both repurposed drugs and emerging tools such as 3D bioprinting and artificial intelligence.
Immunotherapy has found new meaning outside of the usual focus on anti-cancer drugs to a renewed emphasis on anti-infectives. Scientists have always known this but because the return on investment (ROI) and demand for anti-infectives was much lower than for cancer drugs, the public is only hearing about this now as biopharmaceutical companies now prioritise research/investment dollars in drugs and vaccines for infectious diseases.
To put it simply, whenever our bodies see anything that is considered to be a foreign pathogen, an immune reaction is elicited using T cells, which are more commonly known as white blood cells, to engulf and get rid of the bacteria, virus or other foreign particle including a malignant cancer cell. This is why drugs that target the immune system such as AVM Biotechnology’s AVM0703 can be repurposed as anti-infectives. AVM0703 is a repurposed drug that was FDA-approved for medical use at low dosages in 1961 and may potentially be a global health solution for COVID-19 because it is orally ingested and has a long stability/shelf life. Additionally, AVM is currently testing the hypothesis that AVM0703 supercharged immune cell mobilization will reduce lung inflammation, kill COVID-19, and induce long-term immunity. Therefore, rapid clinical development of AVM0703 is expected based on its established clinical efficacy, safety and toxicity data in addition to new US Food and Drug Administration (FDA) guidance on accelerated reviews for COVID-19 therapies.
Excitingly, Roche recently announced that the FDA has formally approved its phase 3 clinical trial for Actemra (tocilizumab), an interleukin-6 (IL-6) inhibitor, in severely ill COVID-19 patients, who have been hospitalized with pneumonia. Actemra was originally approved in late 2018 for the management of moderate to severe active rheumatoid arthritis (RA). In fact, the National Health Commission of the People’s Republic of China already approved Actemra earlier in March 2020 for the treatment of patients infected with coronavirus, who have developed serious lung damage and also have elevated levels of IL-6 in the blood. Of note, IL-6 is typically produced in response to tissue damage and infections.
In the past 10 years, 3D bioprinting companies such as Israeli-based CollPlant Biotechnology and San Diego-based Viscient Bioscience have transformed the fields of regenerative medicine. 3D bioprinting is quite intriguing because it serves as a source for not just vital tissues and organs but potentially as a unique way to discover new therapies without succumbing to the usual animal models. The key to successful 3D bioprinting lies in the identification of an ideal bioink, which should possess adequate mechanical, rheological (resistance to flow), and biological properties of the target tissues, which are essential to ensure correct functionality of the bioprinted tissues and organs. In the case of CollPlant, the company is developing a sustainable, plant-based platform technology via the innovative use of genetically engineered tobacco plants that express recombinant human collagen (rhCollagen). CollPlant’s technology offers several advantages compared to other human / animal sourced collagens, particularly with regard to safety since its “virgin” nature implies that it would show zero immune response.
On the other hand, Viscient is working at the intersection of human 3D tissue technology and multi-omics analysis. Specifically, Viscient is exploring 3D bioprinting as a “clinical trial in a dish” by leveraging 3D-bioprinted and other 3D-tissue models made with lung cells to advance support viral infectivity research and search for an effective therapy against SARS-CoV-2, the novel coronavirus which causes COVID-19. Viscient’s research is indicative of the transformative potential of 3D bioprinting in improving efficiencies in the drug discovery process.
Artificial intelligence (AI) is also being leveraged to improve the discovery of new therapies for infectious diseases by identifying patterns in big data and generating illuminating algorithms. Researchers at the Massachusetts Institute of Technology (MIT) recently announced the identification of a powerful new antibiotic that killed many of the world’s most problematic disease-causing bacteria, including antibiotic-resistant strains, while also clearing infections in two different mouse models.
Search engines driven by AI are becoming increasingly popular in our fight against the coronavirus. For example, Google’s COVID-19 Research Explorer tool when prompted with basic research questions will return a list of research papers with highlighted relevant sections that ease the drug discovery process.
The power of AI as a drug discovery tool is perhaps best showcased by the fact that there are over 200 startups globally who are advancing the state of science, especially infectious diseases via machine learning and AI. Key examples include La Jolla-based Data4Cure whose technology is designed to identify new targets and biomarkers, repurpose drugs and identify disease pathways that may be improved with combination therapy. Germany’s Molecular Health’s AI platform can potentially improve the prediction of drug response and resistance and design more successful clinical trials.
Overall, the forecast for the availability of effective therapies against COVID-19 is still fairly optimistic. This is because the coronavirus does not mutate rapidly unlike other infectious diseases such as malaria. However, by its nature, we expect these viruses to change over time and need to keep optimizing how we treat these diseases as we get more clinical data. Excitingly, a new crop of old drugs are finding novel meaning as anti-infectives and the accelerated drug discovery process is substantiated by new policies by health authorities such as the FDA and emerging technologies inclusive of AI and 3D bioprinting. The biggest barrier to widespread adoption and success would be limited information on the long-term safety of new therapies currently in development, particularly vaccines.
Dr. Sophia Ononye-Onyia is a Yale-trained molecular oncologist and founder and CEO of The Sophia Consulting Firm, a life-sciences marketing and communications consultancy that was established in New York City with the goal of amplifying scientific innovation.