AsianScientist (Feb. 4, 2020) – The ability to harness the body’s immune system is revolutionizing the way we think about disease. Even dreaded conditions like skin cancer are now treatable thanks to advances in immunotherapy, like the development of checkpoint inhibitors that was recognized with the 2018 Nobel Prize awarded to James P. Allison and Tasuku Honjo.
A central part of the immunotherapy toolkit are antibodies, which can bind to their targets with exquisite specificity. At this point, more than 570 antibody-based therapeutics are being investigated in clinical trials, highlighting their immense promise.
In particular, antibodies have the potential to target diseases for which there are currently no treatments available. Chugai Pharmabody Research (CPR) uses proprietary antibody engineering technologies to make antibodies to address these unmet needs. In this interview, CPR’s director, CEO and research head, Dr. Tomoyuki Igawa, shares what makes CPR a great place to advance the field of antibody research.
Q: Why did CPR choose to focus on antibody drug discovery and development?
The use of antibody drugs, which harness the host’s immune defences, has been expanded over the last decade by several scientific breakthroughs. Like gene therapy and personalized medicine, antibody therapy is becoming an important mode of treatment—highly sought after for its specificity to disease agents.
At CPR, we focus on antibody drug discovery and development for two reasons. The first is because antibody drugs can be engineered to create sophisticated therapeutic functions that are demonstrably better than existing treatments. The second reason is that we believe the area has the potential to expand into diseases with unmet medical needs.
Q: What are the challenges of developing antibody drugs?
Although an antibody can bind specifically to a target, there are many drug targets where systemic inhibition or activation induces not only anti-tumor effects but also toxic side effects. Specifically, these side effects prevent us from administering antibody drugs at dosages that are effective against tumor cells.
This issue therefore poses a barrier to drug development. However, through Chugai’s proprietary technologies, we believe that we can overcome this problem. For example, using a technology called the Switch antibodyTM, we were able to engineer antibodies that bind only in the presence of tumor-specific metabolites. This technology allowed us to transform those previously undruggable targets, which have good anti-tumor efficacy but strongside effects, into druggable targets.
Q: What are some of the key technology platforms at CPR?
Chugai, our parent company in Japan and also a part of the Roche group, has established proprietary antibody engineering technologies such as the recycling and sweeping antibodies. These technologies in turn allow us to develop antibody drugs that realize unique modes of action previously impossible with conventional antibodies.
For example, our Recycling antibodies® can bind to multiple targets over its lifetime. Unlike conventional antibodies that only bind once, these antibodies can be recycled after binding to their initial target. This capability thus reduces the dosage required, Improving the convenience and quality of life for patients.
Our Sweeping antibodies®, on the other hand, have been engineered to enhance the removal of bound antibody targets, ‘sweeping’ them from the plasma. We also have bispecific antibodies, like the T-cell Redirecting antibody®, which destroys tumor cells more effectively by linking them to T-cells. These technologies, when combined with our platforms for antibody discovery and optimization—Rabbit B-cell cloning and a designed phage library—enable us to achieve high-throughput and efficient drug discovery.
Q: Which diseases do CPR focus on?
We currently focus on oncology, fibrosis and chronic autoimmune diseases like rheumatoid arthritis. An example is the anti-C5 antibody crovalimab, an antibody drug developed by Chugai Pharmaceutical Co., Ltd (Chugai) in collaboration with Roche, for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). PNH is a disease that causes part of the body’s immune system to attack red blood cells, resulting in severe anemia for patients. The antibody drug, now in clinical trials, will be the first antibody drug to originate from Singapore once it is approved.
Q: What’s next for CPR?
At CPR, we not only aim to develop new antibody drugs with Chugai’s proprietary technologies; we are also working to develop our own novel antibody engineering platforms. Since October 2018, we have established a new mode of treatment that will help define the next generation of therapy, beyond current antibody and small molecule drugs.
Q: What makes CPR a great place to work at?
Our research capabilities depend on our employees. We believe in investing in our employees, providing them with new opportunities to continuously grow, learn and maintain their curiosity for science. Through diverse and open collaborations, CPR strives to inspire its scientists and turn experience into action.
Dr Feng Shu
Principal scientist, CPR
Q: What made you join CPR?
I wanted to learn more about antibody drugs, which was still a new mode of treatment at the time. For me, it felt natural to join CPR as it has some of the best antibody engineering technologies in the world. Furthermore, CPR gives us the opportunity to actively collaborate with academics around the world, improving both medical care and quality of life.
Q: What is the culture at CPR like?
The culture at CPR promotes cooperation and open discussion, granting us opportunities to engage people from different fields and diverse backgrounds. In this way, CPR provides room for us to build innovative solutions and develop new ideas for drug discovery and development.
Asian Scientist Magazine is a media partner of Chugai Pharmabody.
Copyright: Asian Scientist Magazine; Photo: Chugai Pharmabody.
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