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Dr. Michelle M. Chen is a Biotech executive and entrepreneur with extensive experience in business and corporate development, company set up & building, investment, operation, R&D, manufacturing and commercialization. Results driven and passionate about partnership to develop innovative technologies and products to make a difference in human health. Proven success in leadership, partnership, commercialization and R&D. Experience in technologies, rare diseases, oncology, infectious disease, immunology, vaccines, genetic disorders, cardiovascular, and personalized medicine.
In your opinion, how has the Drug Discovery and Development landscape evolved over the years? What are some of the advantages of the current technological evolution?
When I first joined the biotech industry as a bench scientist fresh out of post doctorate training, it was during the time of the genomic revolution. With the completion of Human Genome sequencing and the introduction of DNA microarray, we predicted new biotechnologies would shorten the drug discovery and development timeline, and reduce overall development risks. Well, the reality is that the cost of developing a new drug today is more than 2 billion dollars, up from 800 million dollars in 2003. The success rate of clinical trials has dropped by half, down to 12 percent.
On the positive side, we have witnessed positive impacts of technology innovations, particularly in precision medicine, bi-specific antibodies, antibodyADC development, gene, and cell therapy. Take the bi-specific antibody as an example: 10 years ago, less than 10 percent of the antibody clinical pipeline had bi-specific antibody molecules. This percentage has increased to 25 percent in recent years, with multiple platforms available and 3 approved bi-specific antibody drugs. At WuXi Biologics, we launched WuXiBodyTM bi-specific platform in late 2018. Today we have 12 licensing partners and more than 20 ongoing projects.
I also believe the golden age of antibody-drug conjugates has arrived. I worked on the antibodyADC in the early 2000s when the concept was new. It took the industry a long time to figure out how to control the ratio of toxin and antibody molecules to maximize the therapeutic window. Today, there are 8 antibody-ADC drugs approved by the FDA, 3 of which were approved in 2019 alone! At WuXi Biologics, we also saw an increase in demand for our ADC service. We have built a state-of-art facility in the city of Wuxi in China, to enable both drug substance and drug product manufacturing, and are now working on 28 projects for clients all over the globe.
2. What according to you are some of the challenges plaguing the Drug Discovery and Development landscape and how can they be effectively mitigated?
All stages of drug discovery, clinical development, and manufacturing face unique challenges. From the biological drug discovery point of view, we are limited by the number of good targets to go after and by our understanding of disease biology such as neuro-degeneration. Perhaps new artificial intelligence and machine learning approaches could help us.
Clinical development still carries the most cost and significant risks. I am excited about the development of biomarkers as either companion diagnostic assays or pharmacodynamics tools for precision medicine. For example, when I was at Ventana Medical Systems (a.k.a. Roche Tissue Diagnostics), we partnered with Pfizer to develop an ALK IHC test, which was used to prescreen for non-small cell lung cancer (NSLCL) patients with gene rearrangements. Only these patients, with the ALK gene rearrangements, would potentially benefit from Pfizer’s XALKORI® (crizotinib). The biomarker-based approach could significantly reduce clinical risks so that we can have the “right” drugs for the “right” patients.
As a runner, I like to compare drug development to running a marathon. It is not for the faint of heart
Manufacturing is a very complex process that requires strong engineering skills, rigorous quality checks, and strict SOP adherence. Quite often, the industry does not spend much time discussing the manufacturing risks. In the case of gene therapy, because we are fixing whatever is defective in genes, the biology risk is relatively low; however, manufacturing is at the forefront of risks. The key questions are: Can we manufacture it? How much can we make? What is the titer? Are these productive viruses? How can we make the process more cost-effective?
The pre-existing immunity against some of these viral vectors in gene therapy is another challenge the industry is facing. People are watching the gene therapy trials from BioMarin where I last worked prior to joining WuXi Biologics and Spark Therapeutics. The data should be useful for us to understand the limitation of existing technologies, and find a way to improve them.
3. Which are a few technological trends influencing Drug Discovery and Development today? What are some of the best practices businesses should adopt today to steer ahead of competitors?
I see two important trends where high tech and drug development converge.
One is applying artificial intelligence and machine learning to the drug discovery process. You can model biological processes, pathways, and crosstalk in a neutral network, and let computers do the prediction. Computers are like “dragons”. To use them appropriately, you have to learn how to train the “dragon.” The larger the training sets with associated outcomes, the better. This field is highly interdisciplinary. People with very different backgrounds such as, computer science, data science, physics, math, chemistry, and biology get together to work out a common solution. It is a daunting task but great insights could come out of this interdisciplinary approach.
The second trend is to apply digital health for clinical development. We all know of the importance of biomarkers in personalized medicine. Digital health can take this to the next level. Can we control drug release by using our Apple Watches? How can we use electronic databases and medical records to optimize patient enrollment in clinical trials, to monitor side effects, and to maximize drug compliance? I expect these digital tools will play an increasing role in our drug development journey.
4. Do you have any advice for industry veterans or budding entrepreneurs from the Drug Discovery and Development space?
For the veterans out there, who have witnessed the ups and downs of the industry, my advice is to keep an open mind. 10 years ago, gene therapy was a “forbidden” field. Now it is hot.
For the budding entrepreneurs, my advice is to take your time to learn this industry and do your homework, but do not let the high failure rate in our industry limit your imagination and your ability to innovate. It’s very difficult to develop medicines and pharma is one of the most regulated industries. Patience is also required. As a runner, I like to compare drug development to running a marathon. It is not for the faint of heart.
That said, we should train young people and welcome those who are bringing in new ideas and new tools to transform how medicines are developed. I have interacted with and advised many entrepreneurs. I am confident their enthusiasm and creativity will make a positive impact.