Agatsuma: ADCs consist of multiple parts including a payload, a linker, and an antibody and specialized knowledge about each of them is required to develop a complete medication. That is why, in the beginning, we brought together a team of individuals with varying specialties. Each of the research team members used their own specialty to further the talks, leading to truly lively discussions. In the spirit of true collaboration, we clashed hard with one another precisely because we were serious about achieving results.
Engaging in these frank discussions, however, gradually led to a mutual understanding of each other’s specialty, which in turn gave way to mutual respect. After all, we are scientists and researchers at heart, so with time we naturally gravitated toward a common consensus: the pursuit of that which is best. We truly began to work together as a cross-functional team to pursue our collective outstanding goals.
Starting in the third year of the project, Dr. Abe became the Group leader of the Biologics Research Laboratories, and also became tasked with managing the entire ADC research team..
Abe: Since the research team members had such great passion for their work, their different opinions indeed led to lively discussions on a regular basis. The members were each dedicated to their specialty and took the project very seriously.
The need to bring all these specialties together makes ADC drug development different and more difficult than conventional drug development. We had to look at a very large number of proposed combinations of elements, select the most promising ones, and test hypotheses thoroughly—work that took a huge amount of time and effort. One insight in particular greatly helped move our research forward. Before the merger of Daiichi and Sankyo, Daiichi had jointly developed an antitumor small molecule drug with another drug company. We saw the potential for that compound as a drug for use in our ADC. Using as the foundation the experience and knowledge obtained from a conjugation research conducted at Daiichi in the early 2000s, we synthesized a wide variety of linkers and derivatives of the compound to connect with antibodies, and we evaluated them one by one to achieve the best result.
Agatsuma: Yes, as a result of Dr. Abe and his team’s commitment and dedication, Daiichi Sankyo conducted non-clinical studies that suggested vastly greater efficacy than those of competing compounds created by other companies. When we saw this, everyone in the research team was elated, and they all expressed their appreciation for each other. I attributed this impressive accomplishment to the dedication of our company to create the best drugs possible, as well as our artisan spirit, approaching our research as craftsmen and craftswomen.
Without a doubt, it was the result of amazing teamwork. It was not about following the instructions of any one person. We paid no attention to titles and seniority but rather made it all about science and actual data. Together, we agreed, “If the data are good, then let’s try it.” Our dedication was the driving force, and we produced some great results. This ADC project gave me the chance to reconfirm the incredible research potential of our company.
Creativity and knowledge will be passed down to the next generation of ADC development
Agatsuma: The fruit of our ADC research and development efforts is not limited to our medicine targeting HER2. Another big accomplishment was in our building an in-house technological foundation for ADC R&D, which differs quite a bit from that for small molecule drugs and antibody drugs. In establishing this process, the team leaders from each of the departments played a crucial role.
Abe: From the start of the research, we had the objective of developing multiple ADCs in-house. Thus, in order to engage in R&D for the next ADC drug development candidate, and then the next, and so on, all the team leaders agreed we should establish an entire process for ADC development. In addition, the senior directors from related functions created the ADC management team to provide the researchers with needed support. Its purpose was to determine all the necessary items for research and production, in addition to a clear timeline to help make each researcher’s work as smooth as possible. This collaboration and aligned ways of working contributed to the establishment of our unique ADC R&D process.
Agatsuma: Currently, we at Daiichi Sankyo are pursuing our “3 and Alpha” strategy focused on our three most important ADCs. What’s made this strategy possible is our unique ADC R&D process, which was the result of trial and error and deep dedication to patients. For example, the mindset behind this process encourages us to go beyond our current three core ADCs and look at different payloads. It is a real strength in our research.
Abe: Since we first started our ADC research, we have doubled the number of researchers involved in ADC R&D. Many of the researchers were early in their careers when we experienced our success in developing an ADC to target HER2. They are sure to be the leaders of our “3 and Alpha” strategy going forward.
Agatsuma: Those early in their careers took the opportunity to collaborate and coordinate closely with their more senior colleagues. This provided an excellent chance for more experienced colleagues to pass on their accumulated knowledge and passion for innovation on to the emerging talent at Daiichi Sankyo, who will no doubt continue to be a pillar of strength for Daiichi Sankyo’s future research and further growth. They are a tremendous asset for the company.
Abe: At the start of our research, Dr. Agatsuma and I agreed that the project members should not be concerned whether they originally came from Daiichi or Sankyo before the merger. We all came together under a common purpose for patients. By pursuing our goals without consideration for company of origin, experience levels or other differences, the research team was truly able to create and nurture a unified team. I think Dr. Agatsuma’s exceptional management style helped make this all happen.
I believe that successful drug development does not happen due to a single individual, but because of the collective accumulation of the experience in every scientist and developer involved. It all comes down to the artisan spirit. That is why my challenge now is to leverage my experience to develop the next generation of talent and further raise our drug development success rate. I want to create an environment that makes it easier to come up with the innovations that get new drugs to the patients who need them as quickly as possible.
From around the world, we are hearing through medical institutions from patients whose conditions have significantly improved thanks to our HER2-targeting ADC. This is a huge motivation for taking on the next big challenge.
While Dr. Agatsuma and I are the ones interviewed for this story, I’d like everyone to understand just how many researchers and other participants made our ADC success story possible through their tremendous efforts. I’d like to express my utmost appreciation to them all. Our HER2-targeting ADC embodies the positive intentions and hard work of many, many people.
Agatsuma: Drug development is by no means a single-person effort. It’s also an extremely difficult type of work. And it’s work that is well worth pursuing. Our mission is to help save the lives of as many patients as possible, and we join forces with many colleagues to take on new challenges and leave a global legacy in improving and extending patients’ lives. Nothing could make us researchers happier.
Inheriting the company’s DNA for pursuing drug discovery that gave birth to revolutionary drugs, I hope that each and every researcher at Daiichi Sankyo will continue to carry forward the pride and passions of our work into the future. Not just 5 years into the future, not 10 years, but 100 years into the future.