Astellas Pharma Inc. Recruit

What are your current work roles and responsibilities?

As a non-clinical safety expert, I am responsible for presenting scientific evidence that may affect patient safety at an early stage, after the drug concept has been developed.
Astellas brings cutting-edge science to drug discovery. The most important thing is not whether a treatment is advanced or not, but that patients feel good about receiving it. To achieve this, it is essential to take into account not only efficacy but also safety.
The words of the 16th century physician and chemist Paracelsus “Everything is poison, and nothing is not; only the dose determines what is not poison” sum up the essence of toxicology well. Safety researchers conduct studies that examine all biological reactions in detail and their doses, and interpret the results obtained from various perspectives, including pharmacological effects and pharmacokinetics. I am the profiler who identifies the optimal balance between risk and benefit.
Early in the drug discovery process, I conduct studies to identify critical safety profiles that will have a significant impact on the success of the project. Planning a cascade to select drug seeds from multiple candidates is also essential to establish a safety evaluation system that utilizes new science and technology. Because the speed of drug discovery is extremely fast, we must anticipate the flow of drug discovery and perform optimal evaluations.

What are challenging, interesting, or difficult aspects of your role?

Safety profiling requires a variety of expertise, and while it is important to be familiar with all of them, in practice it is important to have a team activity composed of experts. We constantly consider how to leverage indivisual expertise, work together as a team, and create impactful outocomes. In many cases, we use our expertise in the field of toxicology to develop new evaluation systems using state-of-the-art technology.
On the other hand, the reality is that resources such as time and money are limited in the early stages of drug discovery. In addition, in recent years, the 3Rs* in animals has been attracting attention as a social issue. Drug discovery research needs to be conducted with social issues as well as its own issues in mind, and I sometimes struggle with how to design safety evaluation strategies, but at the same time, I see this as a great opportunity to promote scientific innovation.
As an expert in reproductive and developmental toxicology, I am working on a new study that does not rely on animal experiments. This research has resulted in published results as a consortium study (see also here) and has served as the basis for proposing a new regulatory framework to demonstrate safety. By developing and introducing new evaluation methods, we aim to achieve more effective and reliable safety assessments and further advance the drug discovery process.

*3Rs; Refinement, Reduction, Replacement

What are your current work roles and responsibilities?

In this stage, we are responsible for identifying development candidate from the “drug seeds” which is newly discovered in the Concept Ideation stage. Seeds of medicine are still in the rough in terms of pharmacodynamics, pharmacokinetics and physical properties. We optimize them into the the development candidate, which is more effective and safer for patients.Our works as pharmacology researchers are 1)in vitro/in vivo drug screening based on the knowledge obtained from Concept Validation stage, 2)evaluation of drug efficacy in pathological models that reflect the biology of the disease, etc. The results are shared and discussed with specialists in pharmacokinetics, medicinal chemistry, safety, etc. and utilized in the design of the next candidate product. For small molecules, by continuing the cycle of synthesis-evaluation-discussion, we select only one development candidate out of thousands of compounds.

What are challenging, interesting, or difficult aspects of your role?

There are many rewarding and interesting aspects to working as a pharmacologist in this stage. For example, when we find a drug candidate that shows outstanding efficacy among others. When we are able to construct a better screening system that can predict the efficacy in a pathological model. When the team is planning the next strategy based on the obtained data.... Especially, I find it rewarding to create a development candidate with our own hands, which is the result of every step we take.
I chose this job because I want to contribute to society through the research I love. I am working every day with the image that our products will help patients all over the world.
Of course, in the process, there are many times when optimization does not proceed as expected, and there are also times when trouble occurs in the screening system. I believe that this is not routine work, but work that requires an observant eye and a desire for improvement.

Eri Yamashita's daily schedule

Daily schedule including remote working

All-day office work schedule

What are your current work roles and responsibilities?

In the optimization research of drug candidates, we are responsible for refining the candidates from a pharmacokinetic prospective.
Pharmacokinetic research evaluates how a drug is absorbed, distributed, metabolized, and excreted in the body. While pharmacology and toxicology research evaluate the effect of a drug on the body, pharmacokinetic research evaluates the effect of a body on the drug in a time-dependent ad quantitiative manner. Based on drug concentrations in target tissues, the concept of drug efficacy is supported and appropriate dosages and dose regimens are determined. Drug metabolizing enzyme identification and inhibition data are also used to predict the risk of drug-drug interactions in humans. Based on the metabolite profiling, we contribute to the selection of appropriate animal species in toxicology studies and to the reduction of the risk of adverse effects in humans. Furthermore, we evaluate the relationship between pharmacokinetics (PK) and pharmacodynamics (PD) using data on biomarkers that support drug efficacy. We also incorporate advanced methods such as Quantitative Systems Pharmacology (QSP) and Microphysiological Systems (MPS) to improve the translatability from animals to humans. We are also working to improve the accuracy of our predictions. Through these evaluations, we contribute to the selection of development candidates that minimize adverse effects in humans and maximize drug efficacy. Selected development candidates are then advanced to the Translational Research & Studies for IND/NDA stage, where their profiles are futher investigated.

What are challenging, interesting, or difficult aspects of your role?

In the case of conventional small molecules, methodologies for pharmacokinetic evaluation have been established to some extent, and we are able to understand pharmacological actions and side effects from the obtained data and to predict them in humans. Recently, the drug modalities have been diversifying, including antibodies, viruses, cells, and nucleic acids. Conventional methodologies are not applicable to these new modalities, and there is a lack of knowledge and know-how in the pharmaceutical industry. In these modalities, pharmacology and toxicology data are often important for understanding pharmacokinetics in addition to the target biology . The team is highly motivated to solve each problem together, and we are able to resolve issues through repeated discussions. This is a role that gives me great satisfaction, where we can establish strategies from scratch in a field in which we have no experience and overcome unknown challenges as a team. Why don't you join us and tackle new challenges?

Yosuke Yamanaka's daily schedule

What are your current work roles and responsibilities?

Xue：
As medicinal chemists, my job is to drive the design, synthesis, evaluation, and analysis (DMTA; Design-Make-Test-Analysis) cycle of new drug candidate molecules. This stage is at the core of new drug discovery and plays a very important role.
Based on the target information and initial data obtained in the Concept Ideation stage, the DMTA cycle is executed, and finally the optimized development candidate is handed over to the Translational Research & Studies for IND/NDA stage. We may be responsible for multiple themes simultaneously while conducting parallel synthesis. Improving the efficiency of this stage is a challenge for the entire drug discovery process.
In recent years, AI and robotics technologies have made significant progress. Our team has built a platform that utilizes these technologies to shorten the duration of this stage. Specifically, we are utilizing a wide range of functions, including AI-based compound structure design and generation, optimization of reaction conditions, and prediction of physicochemical and pharmacokinetic properties. The introduction of a robotic synthesizer linked to AI not only enables efficient progression of numerous reactions, but also enables structure-activity relationship (SAR) analysis based on acquired data and comparative analysis with AI predictions. Through these efforts, we aim to shorten the time required to acquire development candidates.

Imaide：
Likewise, as a medicinal chemist, I play a manufacturing role in the creation of new development candidates. I am in charge of setting up the appropriate modality that matches the drug discovery concept, starting from the biology that is highly relevant to the disease. In the Engineered Small Molecules (ESM) department, we focus on degradation inducers. We examine the method of acquiring compounds as a starting point, identify the acquired compounds, and then optimize the molecular structure. When optimizing compounds, it is important to utilize structural biology and understand parameters that are highly relevant to drug efficacy and safety. In recent years, we have also been working on the application of antibody-drug conjugates, which requires a high level of technical expertise to create compounds with more complex molecular structures.
The creation of development candidates with guaranteed physical properties, kinetics, and safety is one of the milestones for advancing to the next stage. In addition, research for the supply of compounds for preclinical studies and the manufacture of compounds for clinical studies can be considered from the early stage when development candidates have been narrowed down, leading to the formulation of a more reliable strategy.
In addition, for validation of a drug discovery concept, we may provide compounds that contribute to the validation. We will discuss how to prove the concept based on the findings obtained in the course of the evaluation and promote the project.

What are challenging, interesting, or difficult aspects of your role?

Xue：
The most rewarding part of this stage is the moment when a compound that we have designed and synthesized shows efficacy in in vitro and in vivo experiments, and we see its potential to ultimately contribute to patient treatment. As a medicinal chemist, I feel a great sense of fulfillment when the molecular structure on the blueprint is transformed into a development candidate through efficient synthesis, evaluation, and analysis using chemical methods integrated with AI and other technologies. Another attractive point is that I am exposed to new knowledge and ideas on a daily basis at the forefront of pharmaceutical research.
On the other hand, I also face many challenges at this stage. For example, the correlation between the activity and structure of a designed molecule often does not show the expected results, and to determine the cause of this, a depth of expertise and flexible thinking are required. In particular, in recent years, the diversification of modalities has made AI predictions difficult to apply in some cases, and improving prediction accuracy requires a continuous supply of appropriate data to the model. Furthermore, multiple research themes (some from overseas!) in parallel, efficient schedule management and smooth communication among the team are essential.

Imaide：
I find it rewarding to be able to design with my own hands what could become a development candidate or even a pharmaceutical product. I work with the image that the compounds I am involved in research will be delivered to patients as pharmaceutical products and contribute to their health and treatment.
In my research, I enjoy the scientific process of finding the seeds of a compound and brushing up the compound. When I make a scientific discovery that is unknown to the world, it is as interesting as solving a mystery. I also enjoy working as one Astellas, a team of professionals working together toward the goal of pharmaceuticals, and the interaction with colleagues in overseas offices provides me with opportunities to gain new perspectives.
Our current challenge is how to control targets that are attractive for the treatment of diseases but difficult to control. Modalities and know-how that can control these targets are in demand. For this reason, we are accumulating knowledge within Astellas and constantly keeping a close eye on global scientific advances as we conduct research. We are constantly striving to meet the challenge of linking scientific advances to pharmaceuticals.

Xue Yunwei's daily schedule

What are your current work roles and responsibilities?

Translational research (TR) is a series of studies aimed at bridging non-clinical research findings to clinical application, encompassing a wide range of activities. We approach TR with the objective of increasing the probability of success of Proof of Concept in clinical development and conduct our research accordingly.
Examples of our TR include the identification of biomarkers to confirm the efficacy of drug candidates in clinical trials and the evaluation of drug efficacy and/or safety using human tissue-derived samples. The mathematical modeling work I am responsible of (please refer to the linked resource) is also an integral part of our TR initiatives. During the concept validation stage, hypotheses for the mechanism of the action of a drug candidate is examined through various experiments. By analyzing these experimental data using mathematical models, we aim to deepen our quantitative understanding. Furthermore, by incorporating species differences between animals and humans into the mathematical models, we are able to predict candidate profiles in humans and contribute to the design of clinical trials. In essence, mathematical modeling is a core TR activity that translates diverse preclinical findings into a quantitative framework and predict clinical outcomes, serving as a true bridge between non-clinical and clinical.

What are challenging, interesting, or difficult aspects of your role?

The application of mathematical models in drug development has a long history. Traditional models, such as pharmacokinetic models, which describe the disposition of drug candidates in the body, and pharmacokinetic-pharmacodynamic models, which capture the relationship between drug exposure and pharmacological effects, have been widely used. In recent years, a new type of mathematical model known as the Quantitative Systems Pharmacology (QSP) model has gained increased attention, and we are actively focusing our effort in this area. QSP models aim to represent the underlying biological mechanisms of disease, allowing us to analyze complex interactions between drug actions and physiological responses. Therefore, QSP modeling requires not only advanced model-building skills, but also a deep understanding of biology. Although this is a very challenging task, I find it highly rewarding to collaborate with pharmacologists in developing these models, and it is an exciting moment the model successfully reproduce the data. These QSP models, once developed, are used for various clinical purposes. Recently, we have been particularly focusing on supporting clinical trial planning by predicting the pharmacological effects of combination therapies involving of our investigational drugs and marketed drugs. Being able to contribute directly to actual clinical development through such modeling work is both interesting and deeply fulfilling.

What are your current work roles and responsibilities?

I have two main responsibilities. First is to formulate the stories and strategies for the pharmacological studies required for investigational new drug application (IND) and new drug applications (NDA). Second is to ensure the reliability of these preclinical pharmacological studies.
The development candidates selected during the Candidate Creation & Optimization stage in each project, are subsequently subjected to clinical trials, where they are administered to volunteers and patients to evaluate their safety and efficacy. To initiate clinical trials, an IND must be submitted to the regulatory authorities in each country with accurate non-clinical data. After long termed clinical trials, an NDA must be filed for a development product that has demonstrated promising results in clinical trials to bring it to market.
In the Translational Research & Studies or IND/NDA stage, we manage to develop the pharmacological study story and strategy, and to prepare a reliable pharmacological study report required for submission in collaboration with the researchers involved in the Candidate Creation & Optimization stage. Our collaboration extends not only internally but also with external resources such as contract research organizations (CROs) and collaborative research to prepare a pharmacological study report. In some cases, we also conduct research to support post-launch product promotion.
In addition, it is crucial to ensure the reliability of non-clinical pharmacological studies, we optimize operational systems and rules to guarantee with reliability, and we provide consultation on all aspects of non-clinical pharmacological studies from study design to report preparation. This includes collaboration with the Quality Assurance department and providing reliability education for researchers.

What are challenging, interesting, or difficult aspects of your role?

Our work to lead up to a drug approval application is the most exciting and challenging. During this period when the countdown begins for a new drug to reaches patients, accuracy and speed are required in our daily work, we deeply consider that each of our work is directly related to the light side for patients, which makes the work both responsible and rewarding. Filing for approval and dealing with the regulatory authorities are responsibilities that are special to a pharmaceutical company, and the ability to learn different perspectives from those of research is also a major attraction.
Another appealing aspect of this role is the many opportunities to broaden your knowledge by being involved in a variety of projects, both in Japan and overseas, which increases your exposure to cutting-edge science. It is very rewarding to be able to bring our expertise together and work as a team to propose drugs to the world that do not yet exist.
In non-clinical pharmacological study, the most important thing is to ensure reliability. Our policy is not only to comply with existing rules but also to optimize operational systems and rules to ensure reliability. So, exchanging opinions with members of research centers around the world is a valuable opportunity for us to learn from each other's perspectives. Exchanging views with pharmaceutical companies is also a valuable opportunity.