Astellas CEO Yasukawa On Enabling Faster R&D
TPDs One Beneficiary
Executive Summary
Keeping the company focus on launching innovating drugs, Astellas CEO Kenji Yasukawa talks in part one of this exclusive interview on how the Japanese firm transformed its R&D processes to allow more flexible and agile decision-making beyond the wall of multiple sections.
Surviving the competition for innovative pharmaceutical products requires swift decision-making in R&D. Kenji Yasukawa, who has been president and CEO of Astellas Pharma, Inc. since 2018, says he felt the importance of this maxim during his 25 years in the firm’s R&D operations.
The Japanese major's ongoing efforts to launch first-in-class candidates faster have led it to success with current mainstays such as big-selling prostate cancer drug Xtandi (enzalutamide). However, Yasukawa told Scrip in an exclusive interview the firm had in fact been going through transition periods to enable faster and better decisions in R&D.
Over the past decade, Astellas has worked to remodel the process, notably encouraging employees to re-evaluate the real necessity of certain meticulous experiments and to discuss the purpose of changing its culture with “over-quality,” as Yasukawa dubbed it.
For example, the firm used to consider multiple demands from internal stakeholders, such as in manufacturing or sales functions, at the very early stage of R&D. This sometimes prevented flexibility or rapid progress to maximize the chance of creating innovative projects. It then urged the staff to prioritize demonstrating successful Phase I results or proof of concept, rather than having to consider such other details first.
The executive - who will become chairman on 1 April and be succeeded as president and CEO by Naoki Okamura - talked about how the company made the improvements and its strategic approach to R&D priorities and goals.
This first part of the interview focuses on the factors behind recent announcements on the addition of targeted protein degraders to its focus areas, while the second part will look at the recent status of key pipeline candidates such as zolbetuximab and fezolinetant, along with gene therapy and deal strategy.
2021 Transformation For 'Agile' R&D
The drive for a more agile and time-sensitive culture is reflected in some recent strategic moves.
In 2021, Astellas transformed several workflows and decision-making rules in R&D, with its research section giving more autonomy to project teams, which consist of members from multiple functions such as pharmacology, safety and metabolism.
However, section managers used to be able to rescind project teams’ decisions after they were made, which Yasukawa found problematic in terms of supporting speedier research. Today, every leader of a research project team now has the authority and responsibility to instruct the path of action beyond the walls of each individual section.
“Team leaders are responsible for leading projects fast. The managers of each research section are responsible for training such team leaders and building the capacity and capability of organizing dozens of projects,” Yasukawa explained.
The firm has led multiple training sessions for project leaders, sharing lists of dos and don’ts for these along with section managers. The success of global R&D projects now largely comes down to the skills of project leaders, Yasukawa noted, pointing out that the creation of successful staff in this role remains one of the hardest challenges for the firm.
As for development functions, Astellas decided to bring forward much earlier the process of designing appropriate trials for investigative new drug (IND) filings. Today, as soon as a go decision for a candidate is decided, the development team joins the research project team to discuss the studies and data required for an IND package, with a focus on speed.
"Development teams used to join the research team six to nine months before IND filing to decide data. Then they started to complain about trials and their concepts, which could cause a year-long hiatus. I really hated it!" - Astellas president and CEO Kenji Yasukawa
“In the old days, development teams used to join the research team six to nine months before IND filing to decide [the candidates’] data. Then they started to complain about trials and their concepts, which could cause a year-long hiatus in development. I really hated it!” Yasukawa conceded, looking back at his own 25-year career in R&D.
One year since the changes and training started, Yasukawa says the R&D process has gained a certain agility in decision-making, especially for Phase I and IIa studies. “Now the development teams join the research teams two years before candidates’ IND filings. I think [our staff] has become much better at refining their ideas of developing projects.”
Primary Focus, AI & Robotics Automation
In its R&D strategy, Astellas has set out five “Primary Focus” areas, which at present comprise immuno-oncology, genetic regulation, mitochondria, blindness and regeneration, targeted protein degradation (TPD). Setting these fields with the aim of continuously launching highly competitive products has been high in Yasukawa’s mind since he served as chief strategy officer before 2016.
Creating and refining competitive products continuously for the global market has been his “primary mission” as CEO, he said. “I think we can be highly competitive in these five areas. Now that our competitors are making progress, we must not stop [ours].”
Recently, Astellas announced TPD as a new primary focus area and disclosed the swift discovery of its lead candidate ASP3082, a first-in-class selective KRAS G12D degrader which has already entered Phase I. At its last R&D Day, the company emphasized how its R&D organization restructuring had expedited decision-making in the discovery process.
Yasukawa told Scrip in the interview that the swift discovery of ASP3082 was also largely enabled by implementing artificial intelligence (AI) and lab automation approaches.
The TPD discovery process requires designing molecules that fit the pocket of the targeted protein. AI helped in the three-dimensional dynamic simulation process of molecule design, then automated lab processes conducting early 24/7 screening.
This combination replaced the previous process that used to take two years until lead candidate nomination, using X-ray structure analysis and manual approaches. Yasukawa credited “implementing such modern technology” for the much quicker progress.
Internal Committee Grants 'Express Tickets'
Another element which has enabled faster internal development is a flexible culture to grant expedited processes for selected candidates, which during the past decade has prioritized some potentially successful assets over others. Yasukawa described the process as “giving express tickets,” which has shortened the time between candidate nomination and IND filings from two years to almost one year.
This approach was used for the TPD candidates, Yasukawa noted, describing the importance of time-sensitivity, given time is an invaluable asset for a pharma firm as well as its human resources and money.
The idea led to the launch of a new R&D project evaluation committee called the “Kachi [value] Committee” in October 2022. This gathers several sections including corporate planning, R&D and finance and discusses investment decisions and prioritization, and the portfolio building of R&D projects, every quarter from various points of views, including development strategies, implementation possibilities and value for patients.
Considering the recent adoption of flexible and faster regulatory approaches for processing innovative drugs in several countries, Yasukawa considers the Kachi Committee will help plan for faster than usual launches by discussing manufacturing or sales promotion at an early stage if necessary.
(Part two of the interview is available here.)