Around 2025, oncology is entering a new phase in which antibody–drug conjugates (ADCs) sit at the center of a much broader competition for the “next decade” of cancer care. In this series, we review the most important recent clinical data and big-pharma deals in ADCs and related modalities, with a focus on what is actually happening now in trials and business development.
In Part 1, we zoom in on AstraZeneca (AZ). Building on the success of Enhertu and Datroway, AZ is trying to create an integrated oncology platform that spans in-house ADCs, radiopharmaceuticals, bispecific antibodies, T-cell engagers and cell therapy. Introductory topics such as basic ADC mechanisms, structural design and payload classes will be covered separately in the upcoming “Beginner to Expert | ADC Intro to the Front Line: A Comprehensive Guide to the 2025 Global ADC Arms Race” series.
How to read this series
The “Recent ADC Landscape Update Series” is positioned as a news-oriented companion to the more textbook-like ADC intro series. Here we focus on pivotal readouts from ESMO, WCLC and other major meetings, as well as on large M&A and licensing deals that shape the competitive landscape. The goal is to give you a concise but concrete snapshot of where cutting-edge ADC development and strategy stand today.
The intended audience includes researchers, pharma R&D and business development teams, CVC and institutional investors, and consulting firms who work with specific companies, projects and trial names in their daily practice. At the same time, we aim to keep the narrative accessible enough for clinicians, students and general readers who want to follow the big picture, by briefly explaining key technical terms where needed.
Why AstraZeneca’s strategy matters in late 2025
AstraZeneca has rapidly become one of the most prominent players in ADCs thanks to its collaboration with Daiichi Sankyo on the HER2-targeted ADC Enhertu and the TROP2-targeted ADC Datroway. These agents are reshaping standards of care in breast cancer and expanding into new indications, while generating blockbuster-level sales.
However, AZ is already looking “beyond Enhertu.” On top of these partnered ADCs, the company is building a diverse in-house portfolio of Topoisomerase I–based ADCs with proprietary linkers, radioconjugates, bispecific antibodies, T-cell engagers and both autologous and allogeneic/in vivo cell therapies. Rather than treating these as separate silos, AZ clearly views them as parts of a coherent oncology platform.
Conceptually, this means focusing less on any single modality and more on finding the best combination of target, payload and format for each biological context and patient segment. In that sense, ADCs are a central but not exclusive tool in a wider toolbox that aims to progressively displace traditional chemotherapy and single-agent immunotherapy.
From Enhertu and Datroway to a proprietary DXd-like platform
Enhertu demonstrated that a well-designed ADC with a Topoisomerase I payload and strong bystander effect can dramatically improve outcomes in HER2-positive and HER2-low breast cancer, even against a strong incumbent like Kadcyla. Datroway extended the same underlying DXd platform to TROP2, opening up new options for triple-negative and HR-positive breast cancer where therapeutic choices were limited.
These successes validated the core idea that potent, membrane-permeable payloads and optimized linkers can generate durable clinical benefit while maintaining manageable safety profiles, despite class-wide concerns such as interstitial lung disease (ILD). For AZ, they also provided a strong rationale to invest in an in-house platform that incorporates lessons learned from Enhertu and Datroway into proprietary ADCs aimed at new targets and indications.
AZD5335 and AZD8205: the backbone of AZ’s in-house ADC platform
At recent ESMO meetings, AZ highlighted two in-house ADCs: AZD5335, targeting folate receptor α (FRα), and AZD8205, targeting B7-H4. Both use AZ’s own linker and Topoisomerase I payload technology and are positioned as the first wave of a broader proprietary ADC portfolio.
In a phase 1/2a trial in platinum-resistant ovarian cancer, AZD5335 delivered overall response rates around 50–56% across the 1.6–2.4 mg/kg dose range, with more than half of patients free from disease progression at a median follow-up of roughly eight months. Importantly, activity was observed not only in high FRα-expressing tumors but also in lower-expression cohorts, hinting at a potentially broader addressable population than current FRα-targeted agents.
AZD8205, aimed at B7-H4, is being developed across several solid tumors including gynecologic cancers and breast cancer. Because B7-H4 is associated with immune suppression in the tumor microenvironment, B7-H4 ADCs may eventually serve as a backbone for combinations with checkpoint blockade or other immunotherapies. From AZ’s perspective, these programs are as much about validating the robustness of its linker–payload platform as they are about any single indication.
Expanding into radiopharmaceuticals: the Fusion acquisition
In parallel with ADCs, AZ is making a bold move into radiopharmaceuticals. The acquisition of Fusion Pharmaceuticals brought in assets such as the PSMA-targeted radioconjugate FPI-2265 for prostate cancer and an EGFR–cMET radioconjugate for solid tumors, along with radiochemistry expertise and manufacturing infrastructure.
Radioconjugates share many conceptual similarities with ADCs: in both cases, a targeting moiety (often an antibody or small molecule) delivers a payload to tumor cells. The key difference is that, instead of a cytotoxic drug, the payload is a radionuclide. AZ aims to leverage its experience in target selection, linker chemistry and payload optimization from ADCs to build a radiopharma portfolio that can provide highly localized radiation while minimizing off-target exposure.
Bispecific antibodies and T-cell engagers as complementary pillars
AZ’s oncology platform also includes a growing suite of bispecific antibodies and T-cell engagers. Examples include rilvegostomig, a PD-1/TIGIT bispecific, and volrustomig, a CTLA-4/PD-L1 bispecific currently being tested in multiple phase 3 trials. These molecules aim to modulate immune checkpoints more efficiently than combinations of separate monoclonal antibodies.
On the T-cell engager side, AZ is advancing CD19×CD3 and CD20×CD3 constructs and exploring conditional activation and masking strategies that restrict strong T-cell activation to the tumor microenvironment. Conceptually, this is analogous to the way ADCs seek to concentrate cytotoxic payloads in tumors while limiting systemic toxicity. Both approaches reflect the same design principle: maximize on-target potency and minimize off-target damage.
A roadmap for cell therapy: from autologous to allogeneic and in vivo
AZ is also building a presence in cell therapy. The acquisition of Gracell added a dual-target BCMA×CD19 CAR-T program for multiple myeloma, while the purchase of EsoBiotec gave AZ access to in vivo cell-therapy technologies that aim to engineer cells directly within the patient’s body.
What stands out is the timing. While several large pharmas are currently scaling back their gene and cell therapy efforts due to cost, complexity and commercial uncertainty, AZ is doubling down. This suggests a long-term bet that ADC-like delivery platforms, radiopharma, bispecifics and cell therapy will ultimately converge into an integrated toolkit for precision oncology, rather than existing as isolated, niche modalities.
Platform vs. single-asset strategies: positioning against other big pharma
Merck’s multi-billion-dollar collaboration with Daiichi on three DXd-based ADCs is a clear statement that ADCs will be central to its post-Keytruda future. BMS is combining checkpoint inhibitors with CELMoD and other agents, and Roche continues to evolve its antibody and cell-therapy franchise. Each company is trying to assemble its own version of a next-generation oncology platform.
AZ’s distinctive feature is its emphasis on investing in the underlying platform—linker–payload chemistry, target libraries and engineering capabilities—rather than relying mainly on one-off deals for individual assets. That approach is designed to give AZ flexibility: as new targets and biomarkers emerge, the company can plug them into existing delivery formats (ADC, radioconjugate, bispecific, T-cell engager, cell therapy) instead of starting from scratch each time.
In other words, AZ is positioning itself less as “the company that owns drug X” and more as “the company that can systematically match targets, payloads and formats across oncology.” If successful, that positioning could be a durable source of competitive advantage beyond the life cycle of any single drug.
Summary: what AstraZeneca’s post-Enhertu era implies
Taken together, AZ’s moves suggest a deliberate shift from being an early leader in partnered DXd ADCs to becoming a broader oncology platform company. Enhertu and Datroway remain critical revenue drivers, but the company is clearly investing ahead of them to ensure that its pipeline can continue to displace chemotherapy and reshape treatment algorithms well into the 2030s.
As many flagship biologics and immunotherapies approach patent expiry between 2028 and 2035, every major pharma is searching for new pillars of growth. AZ’s answer is to place ADCs at the center while simultaneously stitching in radiopharma, bispecifics and cell therapies. That integrated strategy is designed to provide both depth (multiple lines of therapy in key indications) and breadth (coverage across a wide range of tumor types).
For Japanese pharma and biotech players, the key takeaway is not necessarily to copy AZ’s strategy, but to recognize that future competitiveness will depend on the ability to design coherent treatment architectures—deciding which modality to use for which target and patient population—rather than on owning any one modality in isolation.
My Thoughts
Looking at AstraZeneca’s trajectory, what strikes me most is the clarity of its ambition to become an oncology platform company rather than “just” an ADC company. Enhertu and Datroway provide strong proof-of-concept, but AZ is not content to ride those assets until patent expiry. Instead, it is investing in proprietary linker–payload technologies, curated target libraries, radiopharma infrastructure and cell-therapy capabilities that can generate multiple new waves of products over time. Strategically, this is a hedge against the inevitable plateau of any single modality and a way to stay flexible as science and clinical practice evolve. For companies in Japan and elsewhere, the implication is not that they must own every modality themselves—doing so would be unrealistic for most—but that they should think carefully about where they can contribute “sharp modules” into such platforms: for example, best-in-class chemistry for specific payloads, unique biology around certain targets, or execution strength in particular tumor types. Rather than competing head-on with AZ across the entire value chain, building complementary strengths that large players will want to plug into their platforms may be a more realistic and rewarding path. In that sense, the rise of platform-oriented pharma could become an opportunity as much as a threat for focused innovators.
This article has been edited by the Morningglorysciences team.
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