In June 2026, Pfizer received two unsettled news in succession.

Firstly, Chief Financial Officer Dave Denton announced his departure in August - the financial leader who had previously handled key transactions such as Seagen, Biohaven, and Metsera, chose to turn around and leave Pfizer's oncology strategy at the most critical moment.

Four days later, another more impactful news followed, as Pfizer announced the top line results of the SigVie-002 study: the highly anticipated ADC drug sigvotatug vedotin failed to beat the chemotherapy control group docetaxel in a phase III monotherapy trial.
In the context of the rapid retreat of dividends in the post COVID-19 era, this global pharmaceutical giant is undergoing the most difficult strategic reshaping in the history of the empire.

Everything has a reason. This former cosmic pharmaceutical company was completely eliminated in the competition for the first generation immune checkpoint monoclonal antibodies, causing it to almost "lose its voice" in mainstream immunotherapy battlefields such as lung cancer and stomach cancer in the past decade. For this reason, it has spared no expense in expanding with huge debts, establishing oncology, especially antibody conjugated drugs (ADCs), as the core pillar of growth in the post pandemic era.

Three years ago, it acquired ADC leader Seagen at the cost of breaking industry records, attempting to generate eight blockbuster cancer drugs by 2030 and leverage a $10 billion sales increase.

However, the answer was not ideal: the flagship ADC single drug failed, some pipelines were aborted, and billions of dollars in asset impairment followed one after another - this $43 billion gamble was far from fulfilling its returns as scheduled.

But Pfizer has no way out and has no intention of returning to the starting point. The 'golden decade' of PD-1 has been missed. Can it seize the last opportunity in the next generation of tumor immune competition and make a beautiful comeback?

01、ADC monotherapy III clinical setback

As the "star of tomorrow" of pipeline reconstruction in Pfizer's post COVID-19 era, sigvodatug vedotin carries Pfizer's high hopes of breaking the existing impasse in the field of lung cancer ADC.

The drug targets integrin β 6 (IB6), a tumor associated membrane protein with an expression rate of over 90% in solid tumors such as non-small cell lung cancer, and is closely associated with poor prognosis in patients.

As a novel ADC, Sigvotatug vedotin aims to achieve high target selectivity and rapid internalization of IB6, with the potential to reduce binding to normal tissue integrins and decrease off target toxicity.

Previously, there were high expectations from the outside world that it could replace the chemotherapy drug docetaxel, which was first approved in 1996. Pfizer CEO Albert Bourla has stated that the drug "may become a driving force for growth in the later part of this decade"; David Risinger, an analyst at investment bank Leerink, referred to the upcoming data as an "important oncology catalyst" in a report to investors in May.

However, the latest top line results of the Phase III SigVie-002 study (formerly known as Be6A Lung-01) did not bring the expected strategic breakthrough.

This study is a global, open label, randomized controlled trial that enrolled 703 patients to evaluate the efficacy and safety of sigvotatug vedotin compared to docetaxel. The primary endpoint of the study was overall survival (OS), while secondary endpoints included progression free survival (PFS) assessed by blinded independent center review (BICR), confirmed objective response rate (ORR), and duration of response (DOR).

The results showed that compared with docetaxel, sigvotatug vedotin did not achieve the primary endpoint of significantly improving OS in the overall population, and no clear relationship between IB6 expression and response was observed in the exploratory analysis.

Although the overall study did not demonstrate superiority, a strong trend was observed in patients who had only received first-line systemic treatment (approximately two-thirds of the study population) where sigvotatug vedotin outperformed docetaxel in terms of OS and PFS.

In terms of safety, the drug has shown good tolerability and no new safety signals have been found, which is consistent with early clinical research data.

Despite the failure of single drug follow-up trials, Pfizer did not abandon this asset and instead expanded it to earlier treatment lines and combination regimens to maximize its clinical utility.

Currently, Pfizer is actively advancing an ongoing phase III clinical trial to evaluate the combination of ADC and pembrolizumab as first-line treatment for advanced NSCLC patients with PD-L1 overexpression (tumor proportion score ≥ 50%).
In addition, the drug has been explored in combination with PF-08634404 (a novel bispecific antibody targeting PD-1 and VEGF) in early lung cancer and various solid tumors expressing IB6.

02、The hidden pain of the huge acquisition of Seagen

The single drug phase III failure of Sigvotatug vedotin is not only the latest setback facing Pfizer's ADC pipeline, but also further amplifies market doubts about Pfizer's $43 billion acquisition of Seagen and its ADC pipeline value.

In 2023, when the revenue of COVID-19 vaccine and oral medicine is shrinking at a visible rate, Pfizer will purchase Seagen, the "handyman" in the field of ADC, at a price of $43 billion, which will not only break the record of acquisition amount in the field of ADC, but also completely ignite the market.

At that time, Seagen was undoubtedly the global leader in ADC, with 700 patent applications related to ADC drugs, and these patents covered the entire industry chain, including antibodies, linkers, small molecule toxins, etc., making it the company with the deepest technological accumulation in this field.

After the complete acquisition on December 14, 2023, Seagen brought Pfizer four approved ADC drugs, as well as two clinical phase II and ten clinical phase I ADC pipeline assets, including the aforementioned sigvotatug vedotin - which was then codenamed SGN-B6A.

Pfizer's plan is clear: by combining Seagen's advanced ADC technology platform with its global manufacturing and commercialization network, it aims to create at least 8 cancer drugs with the potential to become a blockbuster by 2030, and achieve a $10 billion increase in cancer sales.

However, this "shortcut" that relied on high premium mergers and acquisitions did not give Pfizer peace of mind.

On the contrary, the high integration costs and fierce competition among similar pipelines forced Pfizer to launch multiple rounds of brutal pipeline streamlining between 2024 and 2026, and subsequently swallow billions of dollars in asset impairment losses.
Since the completion of the acquisition, Pfizer has emphasized that 15 clinical assets in Phase I/II have the potential to drive long-term growth, and has specifically named 7 of them. But now, three out of these seven have been terminated from development, and at least five assets have been successively cut off.

Among the abandoned pipelines, many have a similar fate to sigvotatug vedotin - early data was expected, but later clinical trials failed to meet expectations.

For example, Felmetatug vedotin, a highly anticipated Orestatin ADC targeting B7-H4, was once one of Pfizer's eight heavyweight bomb candidates. Phase I clinical trials will commence in 2022, and patient recruitment will cease in December 2024. In February 2025, Pfizer announced the termination of the project based on a comprehensive evaluation of later data and made a provision of $1 billion for impairment.

For another example, Seagen introduced HER2 from Rongchang Biology to target ADC vidicizumab (RC48), which was originally planned to be used for overseas development of bladder cancer and other indications. However, due to the internal pipeline adjustment of Pfizer - especially the strong layout of another ADC drug Padcev in the same indication - Pfizer finally gave up the bladder cancer project of the drug strategically, and accrued about 1.8 billion dollars of impairment in 2024 and 2026 respectively.
In fact, after acquiring Seagen, there have been doubts about whether Pfizer can establish a sustainable ADC pipeline while avoiding the mistakes of Gilead Sciences (Gilead did not launch any new ADCs except for Trodelvy in the six years after acquiring Immunomedicine for $21 billion).

And the single drug phase III failure of sigvotatug vedotin has brought this doubt to its peak - if even the most highly anticipated ADC candidate pipeline fails in critical trials, will the ADC empire, which cost $43 billion to buy, still have a solid foundation?

03、leverages China's dual anti ADC layout

How to truly activate these ADC assets has become a major challenge. Adhering to a single ADC technology route is no longer enough, Pfizer needs to find an immune partner that can synergistically amplify them.

In late July 2025, Pfizer completed an exclusive global (excluding China) licensing agreement with 3SBio, a subsidiary of Chinese pharmaceutical company 3SBio, at an almost crazy price. Pfizer acquired the development, production, and commercialization rights of its independently developed PD-1/VEGF bispecific antibody SSGJ-707 (codenamed PF-08634404 within Pfizer).

This potential transaction, with a total value of up to 6 billion US dollars, set a new historical high for a single overseas down payment of innovative drugs in China at that time, including a non refundable down payment of 1.25 billion US dollars. In addition, Pfizer also injected 100 million US dollars in direct equity investment into Sansheng Pharmaceutical.

Pfizer's positioning of this transaction was unusual from the beginning. It is not a routine pipeline replenishment, but a strategic level "card swap".

At the investor conference call in November 2025, Pfizer's Chief Oncology Officer Jeff Legos made it clear that "we believe PF-08634404 is a cornerstone asset that is highly aligned with Pfizer's oncology strategy. ”He later added that Pfizer is "fully committed to advancing the development of this drug with speed, breadth, and depth at its core.

Speed is the most intuitive manifestation: as of the end of 2025, Pfizer has initiated 7 clinical trials, including 3 phase III studies, and the company plans to launch an additional 5 studies by June of this year.

In terms of breadth, Legos stated that Pfizer is reviewing all existing indications for Merck's Keytruda, assessing entry opportunities one by one, while additionally considering disease prevalence and unmet medical needs. The currently disclosed layout covers multiple major indications, including first-line non-small cell lung cancer, first-line extensive stage small cell lung cancer, first-line gastric cancer, and first-line colorectal cancer.

However, what truly elevates this transaction from a "gamble" to a "strategic hub" is the third consideration - collaboration.
Legos has explicitly stated that the combination therapy with other novel drugs, including ADCs, constitutes the third pillar of its strategy, aimed at truly distinguishing PF-08634404 from similar products.

In this way, Pfizer can use PD-1 × VEGF bispecific antibody as a "new base" for immunotherapy, and combine it with Seagen's retained ADC assets in multiple dimensions to build its own "ICI+ADC" fully self-developed ecosystem.

The sigvotatug vedotin mentioned earlier is an important part. Pfizer has initiated a Phase Ib/II study to evaluate its potential in combination with PF-08634404 for first-line advanced NSCLC - a direct attempt to salvage the asset by combining immune bispecific antibodies after monotherapy failure.

In addition, a phase III study under planning will combine PF-08634404 with the ADC drug Padcev cooperated by Pfizer/Asterai for first-line bladder cancer. The Padcev Keytruda combination has obtained remarkable data in this field - Pfizer's strategy is very direct: replace Keytruda with its own PD-1 × VEGF double antibody, and replicate and hopefully surpass this proven successful combination.
Pfizer is still screening for novel antigens for the next generation of ADCs and researching "multiple permutations and combinations," such as bispecific antibody constructs and novel payloads.

We are not limited to traditional cytotoxic payloads, we are also utilizing our small molecule chemistry capabilities, which can be low molecular weight inhibitors, molecular gels, targeted protein degraders, "Legos said." These can serve as the basis for payloads, delivering very high doses and concentrations of specific inhibitors directly to cancer cells, thereby minimizing safety or tolerability challenges and optimizing treatment indices

This' mix and match 'has already begun. According to Legos, Pfizer is testing another integrin β 6 candidate drug carrying TOPO1 load, which is in the phase I dose increasing stage, and is developing the third intravesical drug delivery molecule with unique load for non muscle invasive bladder cancer as the supplement of Padcev.

Overall, Pfizer's ADC pipeline is advancing in multiple lines - different targets, different payloads, and different constructs - forming a widely covered technical network. And the combined potential of this network and PF-08634404 overlaps with each other, forming the underlying support for Pfizer's impact on its 2030 goals.

This also means that for Pfizer, this dual antibody from China may have already surpassed the scope of a drug under development.
It is a strategic artery that Pfizer has paved for the entire cancer strategy after the flagship ADC monotherapy suffered setbacks and some pipeline failures. It is a strategic artery that can connect Seagen's ADC assets, Pfizer's global development and commercialization capabilities, and the imaginative space of next-generation immunotherapy.

The first wave of Phase III data for PF-08634404 is expected to be read out in 2028. At that time, whether this Chinese dual antibody can truly hold up the ceiling of Pfizer's ADC layout will face its first major test. And the results of this exam will directly determine Pfizer's 2030 goals - whether they are within reach or just a mirage.

reference material:
1.Pfizer Announces Chief Financial Officer Transition
2.Pfizer Announces Topline Phase 3 Results for Sigvotatug Vedotin in Previously Treated Metastatic Non-Squamous Non-Small Cell Lung Cancer
3.STAT，Closely watched Pfizer lung cancer drug falls short in clinical trial
4.FierceBiotech，Pfizer's oncology R&D strategy: Jeff Legos on speed, breadth and novel combinations
5. Looking ahead at Biotech, replacing CFO and failing in the third phase, Pfizer's decline in the era of immunity and ADC
6. Deep Blue View, Pfizer's sky high acquisition of Seagen: Big Pharma strengthens its position after losing its sheep
Is ADC the future of medicine?
8. Same expression, one year after buying ADC giant: Pfizer and its anti-tumor kingdom