In oncology, breakthroughs in treatment are revolutionizing care for cancer patients worldwide. Antibody-Drug Conjugates (ADCs) represent a significant advancement, offering targeted therapies that precisely deliver potent drugs to cancer cells, minimizing damage to healthy tissue. To delve into the potential and ongoing innovation in ADCs, as well as explore strategic partnerships shaping the future of cancer care, industry leaders Partha Anbil, Mike Wong, and Ken Keller, President & CEO of Daiichi Sankyo, discussed key developments. Ken Keller, whose leadership is driven by compassion and a commitment to advancing cancer treatment, shared insights into the latest technological strides in ADCs and the future of personalized oncology care.
Together, they explored emerging strategies in funding, personalized medicine, and novel approaches for hard-to-treat cancers, emphasizing a collaborative vision to transform oncology through innovation, resilience, and strategic growth.
Pioneering the Future of Oncology: Exploring ADC Advancements, Personalized Breast Cancer Treatments, and Innovative Funding Strategies
Partha Anbil & Mike Wong engaged Ken Keller with insightful questions on the evolving landscape of oncology. They explored advancements in ADC technology, personalized approaches for treating complex breast cancer cases, and innovative funding strategies to drive oncological research forward. Mr. Keller provided valuable perspectives on these pivotal topics shaping cancer care.
At the recent ASCO annual meeting, you discussed the potential of transforming Antibody-Drug Conjugates into a more broadly used treatment option. Could you share your insights on the latest advancements in ADC technology and their future potential in oncology treatment? What are some innovative approaches being taken in the industry to enhance the efficacy and safety of ADCs?
Ken Keller: Antibody-drug conjugates, while conceptually nearly a century old, have experienced resurgence and substantial progress in recent years. The initial approval of Mylotarg in 2001 marked a beginning; however, the journey since then has been marked with setbacks, leaving ADCs as a field often perceived as an unfulfilled promise. It wasn’t until a decade ago, as we embarked on our own DXd-ADC research at Daiichi Sankyo, that a shift occurred, resulting in what is now recognized as a revolutionary era in oncology.
Today, ADCs are among the most promising areas of cancer research, capturing the focus at every major oncology meeting, from ASCO and ESMO to the San Antonio Breast Cancer Symposium. With 13 approved ADCs on the market and over $100 billion in recent M&A directed toward ADCs, we’re witnessing an unprecedented level of investment and research momentum.
Our unique DXd-ADC technology, centered around a cleavable linker highly stable in plasma but able to release its payload specifically in cancer cells, has been instrumental in this transformation. This advancement allows us to selectively deliver cytotoxic agents directly to the tumor microenvironment, designed to spare healthy cells and enhance treatment efficacy.
Our pipeline now includes DXd-ADCs targeting HER2, HER3, TROP2, CDH6, B7H3, and other tumor antigens. These ADCs are designed to leverage our innovative payload and linker technology, which we hope will represent a paradigm shift in targeted cancer therapy. But I believe that the future holds even more possibilities.
In the coming five to ten years, we expect to see advancements such as bispecific ADCs targeting multiple antigens, and dual-drug ADCs with payloads engineered to address resistance mechanisms. This approach is rooted in the concept of multi-agent chemotherapy combinations that have historically driven success against various cancers. Moreover, the industry is exploring pro-body drug conjugates, which seek to mask the ADC from the immune system until it reaches the cancer site to minimize off-target effects and optimize efficacy. New payloads will also emerge, incorporating chemotherapy, immune-stimulatory agents, and protein degraders. With these innovations, I envision a future where ADCs supplement traditional chemotherapy and may eventually replace it in many contexts. The major advantage of ADCs is their ability to deliver chemotherapy directly to the cancer site, thereby significantly reducing systemic side effects. Unlike conventional chemotherapy, which affects all rapidly dividing cells, ADCs target only cancer cells, sparing healthy cells and minimizing adverse effects like hair loss and low white blood cell counts.
One example of our success is Enhertu, a HER2-targeted ADC that has redefined breast cancer treatment with five approved indications, including metastatic HER2-positive breast cancer. In the broader scope, the potential of our ADC technology is monumental, with treatments like Enhertu already improving lives and extending the survival of more than 100,000 patients worldwide.
We are actively working on early-stage breast cancer studies, with hopes that our innovations will soon move beyond treating advanced cancers to potentially curing earlier stages of disease.
You previously spoke about the “Faces of Breast Cancer” and the importance of diverse treatment approaches. What novel technologies or innovative treatment strategies are being explored to address the varied needs of breast cancer patients, especially those with unique or resistant forms of the disease? How is the industry approaching personalized medicine in this context?
Ken Keller: Today, I see a few primary advancements in ADC technology driving this potential forward in oncology when it comes to addressing recurrence and resistance:
First, the focus is on targeting diverse antigens to address resistance. For example, our medicine, Enhertu, targets HER2-positive metastatic breast cancer and has shown efficacy in HER2 low-expressing tumors as well. However, a significant challenge is that, as cancers progress, they may lose target antigen expression, leading to resistance. A potential approach to overcome this is by sequentially targeting multiple antigens. If a patient develops resistance to a HER2-targeting ADC, they could transition to an ADC targeting Trop-2 expression, potentially moving to a third ADC that targets HER3. This sequence of targeted antigens enables clinicians to pivot treatment based on the evolving biology of the tumor, potentially extending efficacy over time.
Second, developing ADCs with varied payloads can help overcome resistance while retaining the same antigen target. For instance, resistance can occur due to decreased sensitivity to a specific payload. We want to offer alternative therapies when resistance arises by introducing ADCs with different payloads targeting the same antigen. At the European Society of Medical Oncology (ESMO) meeting, we recently shared phase one data on our novel ADC platform, DS-9606, which utilizes a different chemotherapy payload, a modified PBD. This payload was specifically developed to address cases where our current DXd payload is ineffective, offering a second option that could reinstate sensitivity.
The evolving oncology landscape now enables ADCs to be paired with immune-oncology drugs, such as KEYTRUDA, other ADCs, or even small-molecule therapies. By drawing from past successes in combination therapies, we aim to refine ADC applications as we move these drugs from later-stage to earlier-stage cancer treatments. This strategy leverages a wealth of historical clinical knowledge, strengthening each new wave of therapies. Ultimately, the approach of pairing ADCs with complementary treatments represents a more efficient, targeted delivery of chemotherapy that builds upon many decades of oncology innovation.
Another crucial element of this collaborative effort is partnership. Oncology has always been a cooperative field, and no company can achieve breakthroughs in isolation. By aligning our expertise with trusted partners like AstraZeneca and Merck, we combine our resources and knowledge to develop transformative solutions, leveraging the strongest elements from each organization. This collective approach exemplifies the “Ultimate Team Sport” in oncology: while there is competition, our shared mission to advance cancer treatment remains a collaborative endeavor across the industry.
Our partner, AstraZeneca, presented compelling findings at the World Congress on Lung Cancer on a novel AI-driven biomarker strategy called Quantitative Continuous Scoring (QCS). QCS leverages computational digital pathology to measure antigen expression both on the cell surface and within the cytoplasm, a process traditionally limited to surface measurements. This AI-augmented technique enables us to pinpoint patients most likely to respond to our ADCs, including Dato-DXd, offering a promising tool for enhancing patient outcomes in challenging cases like non-small cell lung cancer. Such technological advancements could revolutionize patient stratification, allowing us to extend treatments to those who would benefit the most while optimizing efficacy.
During the FTPharma and Biotech Summit, you highlighted the need to adapt funding strategies to respond to a changing industry landscape. What innovative funding models or strategies are most effective in addressing the challenges of increased competition and the growing demand for new treatments in oncology? How can companies adapt their financial planning to support sustained innovation and growth?
Ken Keller: I’ll provide a specific example from Daiichi Sankyo, which can shed light on how evolving regulations impact funding strategies, especially in oncology.
Recently, the United States implemented the Inflation Reduction Act (IRA), which fundamentally changes the financial dynamics for drug development by placing a cap on the value lifecycle of a drug. Specifically, it allows the government to set prices nine years after a medicine’s first launch in the US for small molecules – or eleven years for biologics. After this period, regardless of the remaining patent time, the government has the authority to negotiate pricing, essentially instituting government pricing in a relatively short timeframe.
This new regulatory landscape creates unique challenges for oncology drug development. For decades, oncology drugs have followed a methodical development path, beginning in late-stage metastatic disease and gradually progressing to earlier treatment lines as evidence accumulates on safety and efficacy. Typically, initial trials are conducted with patients in urgent need who have already exhausted several lines of therapy. Once safety and potential benefits are established, the drug moves from fourth- or fifth-line treatments to second- and first-line metastatic therapies, eventually targeting early-stage disease where it may offer curative potential.
However, under the IRA, this traditional development path will no longer be feasible for many medicines. Suppose we proceed sequentially from late-stage to early-stage trials. In that case, the nine or eleven-year period can elapse before the drug reaches early-stage indications, effectively shortening the drug’s viable commercial lifespan.
Thus, the need for faster development becomes critical, with only two primary strategies available: accelerating study timelines and conducting trials more concurrently.
Conducting concurrent studies involves higher risk since it requires initiating trials with less information and a higher likelihood of failure. To mitigate this risk, we engaged partnerships with larger companies that have the resources to scale trials more quickly.
In terms of innovative funding models, this need for speed and risk-sharing has driven early-stage companies, particularly those without the extensive resources of a Merck or AstraZeneca, to consider earlier alliances with larger companies. Mergers and acquisitions (M&A), as well as drug partnerships, are becoming more prominent as companies seek to leverage larger firms’ capabilities to stay competitive in this accelerated environment. Essentially, we’re witnessing a shift where partnerships and collaborations are not only a strategic choice but, in many cases, a requirement for sustained innovation and financial viability.
In addition, synthetic control arms are playing a vital role in single-arm studies, especially for accelerated approvals. In the United States, the FDA has been highly supportive of this approach, which permits approvals based on single-arm trials for patients with urgent unmet needs. By using synthetic control arms, companies can compare single-arm study results with real-world standard-of-care data, providing a benchmark without the need for traditional randomized control groups. This pathway enables faster time to market, offering new treatments more swiftly to patients who need them most.
Wrapping Up
Mr. Keller’s insights highlight the profound shifts in reshaping oncology drug development and funding models. The Inflation Reduction Act has introduced challenges and opportunities, urging companies to adapt swiftly by accelerating clinical timelines and forming strategic partnerships. Innovative funding approaches, such as early-stage collaborations with larger firms, are becoming essential for managing financial risk and expediting drug availability. Additionally, the increasing use of synthetic control arms offers a pathway for faster patient access to groundbreaking treatments.
As the oncology field navigates these changes, a blend of agility, partnership, and regulatory innovation will be critical for advancing effective treatments and sustaining growth in a competitive market.
Bios
Ken Keller serves as Chairman of the Board, President, and CEO of Daiichi Sankyo, Inc., and Global Head of the Daiichi Sankyo Oncology Business. Leading a team of dedicated professionals worldwide, Ken is committed to developing life-changing medicines that extend and improve lives. Daiichi Sankyo combines cutting-edge science with deep compassion, focusing on innovative solutions for cancer patients. Ken considers it an honor to drive the company’s mission of creating a transformative standard of care for present and future generations.
Partha Anbil is a Contributing Writer for the MIT Sloan Career Development Office and an alum of MIT Sloan. Besides being VP of Programs of the MIT Club of Delaware Valley, Partha is a long-time life sciences consulting industry veteran, currently with an NYSE-listed WNS, a digital-led business transformation company, as Senior Vice President and Practice Leader for their Life Sciences practice.
Michael Wong is a Contributing Writer for the MIT Sloan Career Development Office and an Emeritus Co-President and board member of the Harvard Business School Healthcare Alumni Association. Michael is a Part-time Lecturer for the Wharton Communication Program at the University of Pennsylvania and his ideas have been shared in the MIT Sloan Management Review and Harvard Business Review.
