Daiichi Sankyo first approached me in 2015 with a potential opportunity in global oncology development, and I listened carefully as they explained how they intended to define oncology as a primary focus. I was aware of the company’s strong research in antibody-drug conjugates (ADCs), which [are designed to] deliver chemotherapy directly to the tumor, thereby minimizing the impact on healthy cells. The leaders at Daiichi Sankyo were interested in further leveraging this portfolio to deliver greater value to patients and stakeholders, so I suggested a fundamental change: the creation of a global R&D position in oncology.

In an interview during the 2017 annual meeting of the American Society of Clinical Oncology (ASCO), which took place June 2nd to 5th in Chicago, Illinois, Peter Hofland, Ph.D., and Sonia Portillo, sat down with Antoine Yver, MD., MSc, Executive Vice President, and Global Head, Oncology Research and Development at Daiichi Sankyo to talk about Daiichi Sankyo novel antibody-drug conjugate, DS-8201, and how this investigational drug has demonstrated a favorable safety profile and promising antitumor activity. [Click to listen]
Clearly, we were on the same wavelength, because in a follow-up conversation three months later they had completed a reorganization and had a new offer related to it. While therapeutic area-specific research and development are traditionally separated in the pharmaceutical industry, Daiichi Sankyo had decided to unify the company’s oncology research and development functions to stimulate rapid decision-making. This was a welcome challenge, as it meant true end-to-end accountability and the opportunity to implement the agile approach I was convinced was essential to success. I was all in.

Along with the value of the ADC portfolio, the company’s unique strengths were clear—even clearer from the inside of the company than from the outside. The power of Daiichi Sankyo’s science is absolutely peerless in the world—the company was sitting on pharmacological and protein engineering solutions that no one else had, and this competitive advantage emerged from another, a more fundamental one: human power.

In Japan, Daiichi Sankyo attracts top scientists from top Japanese universities every single year and employs them for life. Finally, the company is committed to a long-term perspective and subsequently announced its 2025 Vision – a concrete example of this. My sense at that time was that it was the right moment to assert these Daiichi Sankyo strengths globally.

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Compelling data
When I joined the company in April 2016, our HER2-directed ADC, trastuzumab deruxtecan (Enhertu®; DS 8201), was not scheduled to be submitted for approval before 2023, but we began to move forward quickly together. The data were so compelling that we were able to convince the organizers of a major oncology conference to accept a late-breaking abstract for a paper on the new project two months after the conference’s official submission deadline, a clear sign of broad interest in our work.

I then went to the Daiichi Sankyo Board of Directors to persuade them to accelerate plans for our HER2-directed ADC’s development. Assuring them that it was a drug with genuine potential, I urged that, even as clinical trials were being meticulously completed, manufacturing plans for the HER2-directed ADC should be moved up significantly. And indeed, that urging was put into action and as a result, our HER2-directed ADC was submitted and then received approval in the United States in 2019. Thanks to this timely investment, the key manufacturing objectives were achieved the same year, precisely meeting the accelerated milestone!

Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology R&D, Daiichi Sankyo, and José Baselga, MD, Ph.D., Executive Vice President, R&D Oncology, AstraZeneca collaborating in oncology R&D.

Looking for a strong partner
It was clear that our HER2-directed ADC had very strong potential. It was also clear that a strong partner could help achieve a greater scale and fully realize the potential of the new drug. The decision to collaborate was the right one, and it led in 2019 to a landmark global development and commercialization agreement with AstraZeneca.

Meanwhile, pre-clinical stage work on the second ADC, a HER3-directed agent, continued, and we made the decision, unwelcome at the time to shift the focus of the project from breast cancer to lung cancer. We changed course nearly overnight. The team realigned to the decision with agility.

Our reward as a company came in July 2020 with another major global agreement with AstraZeneca for a trophoblast cell-surface antigen 2 (TROP 2)-directed ADC, DS-1062. The two deals are the largest ever struck in the pharmaceutical industry for non-approved drugs, and the value of Daiichi Sankyo has appreciated accordingly.

AstraZeneca’s investment and collaborations on our two lead ADCs allow us more time and resources to develop other potential medicines in our pipeline. But most importantly, our collaborations will help us develop these medicines in more potential indications, bringing the promise to more people with cancer.

Leading through influence
The culture at Daiichi Sankyo has always been built on a foundation of rigorous, systematic scientific endeavor. I felt that leveraging this strength would require a kind of ruthless approach to the prioritization of our research and development programs.

The very first thing I did was to deprioritize some projects which were well regarded within the company, while super-accelerating other projects. We replaced an emphasis on sheer numbers of candidate drugs with a commitment to select the best of the best and develop a certain number of drugs within a fixed span of time.

Essence of leadership
I believe the essence of leadership is in providing focus and being an influencer. That’s why only one month after arriving, I launched an internal project called Cancer Enterprise. In this situation, the term enterprise is defined as a project or undertaking, typically one that is difficult or requires effort and initiative, and resourcefulness.

The key goal was to shift from a focus on job descriptions and remits to a focus on company-wide alignment on project deliverables and for the oncology pipeline. The new “Enterprise” was intended as a platform of influence, and named to indicate two things: first, a sharp focus on therapies for cancer patients; and second, truly entrepreneurial accountability.

Ambition is critically important in our work, and it has to be well directed. You need an extreme focus on doing what has to be done and on doing it well because you can influence so many patients’ lives just by excelling in your job. At the same time, it’s important to aim high to make sure you’re taking on the most important problems and addressing them with the correct angle of attack. In the oncology area, we are constantly adjusting—to the regulatory environment, the competitive environment, and to what we discover in our own science and clinical trial data. We’re constantly optimizing the endeavor to fit the obligation, and that requires real agility.

Fulfilling an obligation to the world
Commitment to quality of science and a mandate to pursue the research where it leads is what makes Daiichi Sankyo the company it is today. We are much more than an ADC company. We have a phenomenal research and drug discovery engine, and we need to feed that engine with the right fuel. In other words, we need to ask the right questions and find the right answers. We have a robust pipeline and are always focused on making the next pharmaceutical products that can change patients’ lives for the better.

The starting point’s challenge is always a biology question and an unmet medical need. But the key is how do you address those with unique and outstanding pharmacology, applying the molecules you’ve designed to influence that biology. That’s what we do.

I believe Daiichi Sankyo has drawn on the traditional strengths of its Japanese origin in achieving global success. Our trailblazing achievements in ADCs are drawing attention to how powerful these smart chemotherapy drugs can be. At the center of a massive trend that may define the next decade, we are now in a position to influence science worldwide, which in turn can generate value for patients and for the company and its stakeholders. With our success comes an obligation to deliver the full value of our science to help more patients worldwide.

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