Astellas Pharma Inc. Recruit

What kind of division is “Engineered Small Molecules (ESM)”?

Hayakawa Astellas has four drug discovery technology/modality axes: small molecule drugs, antibody drugs, cell therapy drugs, and gene therapy drugs. We are in charge of one of these areas called “small molecule drugs.“
We are responsible for drug discovery, including similar technologies, with a particular focus on targeted protein degradation, one of our “Primary Focus” areas of research and development. Currently, ESM has expanded to three bases in Japan, the U.S., and the U.K., and is promoting next-generation small molecule drug discovery research.

ESM is an organization that originally originated from a project called the Virtual Venture Unit (VVU)?

Hayakawa Yes, VVU is an unprecedented and unique initiative. When it was launched in 2019, pharmaceutical companies, including Astellas, were unable to compete in terms of speed with the many drugs and the seeds of drugs coming from biotech companies.
As a breakthrough, a VVU attempted to create a mobile organization. The maximum number of VVU members was 20, and participants were recruited by hand-raising systems. And it took the form of a secondment from the organization to which they belonged.

Why did Sato-San and Morikawa-San join VVU?

Sato I have been involved in research as the pharmacologist^※ since I joined the company. I raised my hand because I wanted to continue working on a program that I had been working on in my department and that was to be taken over by Hayakawa-San's VVU. Another deciding factor was that even as a young man in my fourth year with the company, I was entrusted with the role of theme leader.

Hayakawa The program at that time was a joint research project with the National Cancer Center.
It was a challenging research to identify cancer drivers, and I was impressed by the solid presentation she made at the monthly meetings. I had never worked directly with Sato-San before, but I found her to be a young but driven person, so I asked her to join my VVU.

Morikawa My specialty was synthetic organic chemistry and cancer research, so I wanted to join Hayakawa-San's VVU because it was the most compatible. I was also attracted to Hayakawa-San's leadership style as I gained experience as a chemist^※ under him since I joined the company. He actively transferred authority to the researchers, and I felt his attitude of trusting and valuing the members.
And he said “I just want to attract people with high synthesis ability.“

What is “high synthesis ability”?

Morikawa Perhaps it has two meanings. The first is “creativity” in creating compounds with complex structures in an innovative way. The second is “imagination” to come up with molecules that excite people who see them. In my third year with the company, I had the freedom to think outside the box, so I thought I could make use of that ability as well.

Hayakawa Morikawa-San's idea shined from the beggining. At that meeting during his second month with the company, he suggested that for existing compounds that have the effect of relaxing the bladder and increasing its volume, “it could work for presbyopia if it can relax the muscles.” I was amazed at his ideas! Among the other VVU heads, I was the only one with a chemistry background, so perhaps I had a particular advantage in terms of identifying excellent chemists.

※PharmacologistIt is a position that focuses on pharmacology testing of candidate compounds to verify the efficacy of the compounds. ※ChemistMedicinal Chemist (Drug Discovery Chemist). It is responsible for the formulation of drug discovery programs, the identification of candidate compounds for development, and the design and synthesis of compounds.

What are the deciding factors in choosing members?

Hayakawa First, I judge whether they have clear strengths. Even if people have some weaknesses, they can further develop their strengths by covering for each other with others. The other deciding factor is whether they are cooperative. As with other departments, drug discovery can never be done alone.

Morikawa In order to demonstrate cooperation, it is important that the members share the same goals. In VVU, leaders such as Hayakawa-San showed us a clear direction, saying, "We will do this for the patients" and "We will solve this because it is lacking."

Also, while ordinary organizations are a collection of people in the same profession, ESM and its predecessor, VVU, are teams made up of people with various specialties. In that team, we were required to have a broad knowledge of drug discovery in addition to our own fields of expertise, and to cooperate with each other with mutual respect.

Hayakawa I think that is why the members grow so quickly. Because we are a group of diverse experts, individuals are often entrusted with a lot of responsibility, and there are many opportunities to understand others. On the other hand, there is also the problem that the workload becomes large because we have to do everything oneself.

Was the establishment of VVU and ESM a new challenge for Astellas?

Hayakawa Yes, they are. They are a new style of organization that combines the stability and capital strength of pharma with the innovative mobility of biotech.

I consulted with the CEO of a prominent American biotech company when we were launching the company, and he was skeptical that it would work. I think this is an initiative that has never been seen before in the industry.

Is that the soil in which new discoveries are born?

Hayakawa That's right. A prime example is ESM's lead program, ASP3082. The target of this drug, KRAS^※, is known as an important cancer-related gene mutation, but it has been called an undruggable target and no countermeasures have been found for over 40 years.

The development of ASP3082 began with a casual conversation with a member named Yoshinari-San, the key inventor. He was one of our talented researchers, and the idea was born from letting him move freely and seeing what he came up with. The shape of the molecule that became the prototype of ASP3082, which he told me about, was very beautiful and struck a chord with me. From there, I made the decision to invest resources and proceed with the research, and with the support of those around me, we were able to reach the IND application in just two years. It normally takes 6-7 years, but we were able to get there in less than 1/3 of the time. As far as I know, this is the fastest in the world.

Was it an unprecedented speed?

Sato The fact that the research on KRAS inhibitors and the research on targeted protein degradation-inducing compounds, which were originally conducted in different departments, were combined into one department greatly contributed to this. This was a case that came to fruition because of our groundwork as a pharmaceutical company.

Hayakawa ASP3082, which Yoshinari-San discovered, targets KRAS called G12D, but Morikawa-San then discovered a compound that targets G12V. This is also a protein related to a disease that has been said to be impregnable, and I am witnessing young talent blooming one after another.

In a hierarchical organization, it is usually necessary to obtain mutiple approvals to put an idea into action. However, because we are a small organization of about 15 people, and I, as the head of the department, was able to immediately put it into action, we were able to realize this groundbreaking innovation in a short period of time.

※KRASIt is one of the RAS oncogenes and is the most frequently found in human cancers. KRAS mutations are found in approximately 30% of lung adenocarcinomas in Europe and the United States and approximately 10% of lung adenocarcinomas in Japan.

What kind of work are you currently in charge of at ESM, Morikawa-San and Sato-San?

Morikawa Continuing from VVU, I am the KRAS-related program leader. I have begun to examine the possibility of combining targeted protein degraders we have obtained so far with antibody modalities, and in addition, I have recently been working on validating the possibility of making them into oral drugs that are more convenient for patients. Drastic changes have been taking place in the field of research over the past few years, and what was a theoretical idea a year ago is now a reality. For example, it is now technically and pharmacologically feasible to attach targeted protein degrader to antibodies, and the capability and individual skills of researchers to prove their usefulness have increased. I strongly sense that we are at a major turning point.

Sato I am currently in charge of the KRAS degrader programs and also serve as the program leader for targeting molecules other than KRAS. Being in charge of multiple programs means dealing with a wide variety of competing compounds, which expands the scope of my work and gives me an enormous amount to learn. However, we have a system that allows us to access a database containing many research papers and clinical product information from our competitors, so we can catch up efficiently.

I took maternity and childcare leave twice and was able to return to work smoothly with the support of my colleagues. Although I was anxious, I am motivated by my continuing responsibilities as a program leader.

Hayakawa-San, is there anything you are focusing on in terms of management?

Hayakawa First, I emphasize individual talent. By focusing on the individual strengths of the members who participated through voluntary by hand-raising systems, it have gathered world-leading talent.

The second is to make the most of our talent in a flat organization. I have drastically eliminated meetings and reports that could interfere with research activities. In addition, to ensure the psychological safety of being able to speak freely, I have made it so that only members of the organization to which we belong can participate in meetings. It takes courage to put forward an idea that has just occurred to them. And while I provide a major direction, I actively delegate authority so that individual members can freely expand their ideas. The fact that each member accepts each other's individuality, and that a culture of adopting good ideas regardless of who says them, is also the foundation for lively discussions.

Third, most important as a head, is to try to communicate our research activities to the outside research organizations in an easy-to-understand manner. As a new organization, it is not easy to get people to understand its value. One major difference, especially between the research department and the rest of the organization, is that there is not a high success rate for any one task. Some research starts with finding an uncertain target, and out of 10 research activities, only one can achieve its goal. In the business world, we tend to think that it would be better to focus resources on the one with a high degree of certainty, but this does not work easily in research. I need to communicate our potential and future value to management and stakeholders so that we do not lose rationality from a strategic point of view, while at the same time avoiding the seeds of innovation.

Sato Hayakawa-San assigns leadership roles based on suitability, regardless of an individual's tenure, and respects their decisions. This approach permeates the organization, fostering an environment where everyone is receptive to good ideas and treats each other with respect.

Morikawa ESM encourages open exchange of ideas regardless of position or seniority. For example, a discussion led to the idea of screening compounds with a new approach, which was implemented as a team effort with support from other functional units. This resulted in more promising outcomes. Embracing change and generating new ideas have demonstrably led to tangible results.

As a program leader, I also lead more senior members, but the flat organizational structure ensures smooth communication. Our superiors take the initiative to pave the way, which fosters trust throughout the organization and serves as a significant role model.

Do you feel any difficulties unique to ESM?

Morikawa The unprecedented speed and agile nature of our research often require making A or B choices before results are available. It's a significant challenge to make courageous decisions, considering potential risks and preparing recovery scenarios in case of incorrect choices. Occasionally, there are disagreements within the team. Since different expertise and roles naturally lead to different priorities, we make the best choices by considering various perspectives, such as prioritizing safety or enhancing efficacy.

Sato The speed is indeed much faster compared to other departments. Decisions like "Let's stop this program and focus on this one" are made swiftly. The ability of individuals to move with high mobility even when entering from a different program is unique to ESM.

Morikawa While there are business challenges, the most difficult aspect is the research program itself. Working with the modality of targeted protein degrader and aiming for undruggable targets is a high-level challenge. Our ultimate goal is not just to create drugs but to "cure patients' diseases," which demands constant innovative thinking. Our leaders create an environment that allows us to focus on this, which is invaluable.

What are your future plans and prospects?

Sato ESM has only been able to IND target protein degrader compounds for KRAS, so we would like to apply the technology to other themes that we are in charge of.

Morikawa With our three bases in Japan, the US and the UK, I aim to leverage our diversity to further advance drug discovery research at ESM. As "One ESM," I will continue to create drugs that meet global expectations and contribute to healthcare across various fields.

Also, ESM is still a very high-level agile organization, but we are looking forward to another level of evolution. Right now, we are progressing based on "this is what I want to do," but if we have more individual discretion and ability, I think we could reach the stage of "this is what I have tried." Innovation is a number of moves, so my next goal is to create an environment where we can experiment with even more ideas.

Hayakawa They are fantastic. From a management perspective, I want to make this happen. Currently, I am focusing on the efficient operation of our expanded organization, but I intend to prioritize personnel development next. While Japan currently excels in knowledge and techniques related to targeted protein degrader, researchers in the US and UK have strengths in presentation and communication skills. I want to develop more personnel who can play central roles at each location.

Finally, what motivates you to do your work?

Hayakawa Hearing patients and their families say, "We hope innovative drugs will be developed from Astellas." is my greatest motivation. There are cases where drugs are effective temporarily but the cancer could adapt within a few months, so we are also conducting research to overcome this.

Witnessing the growth of our members is also a source of joy. I watch over them, hoping they will become outstanding individuals who will support the next generation.

Morikawa While the desire to "help patients" is a strong motivator, the fundamental driving force is "enjoyment." ESM is filled with enjoyment, such as the opportunity to dedicate myself to this research with these members in this organization. I look forward to Mondays with eagerness.

Sato Witnessing positive results from taking on new challenges is a moment of great joy. I want to continue making new discoveries in an environment where I can freely engage in my work.