Is BioNTech finally breaking out of its COVID shadow? The case for its oncology comeback

BioNTech SE (NASDAQ: BNTX) may have made its name as the mRNA vaccine innovator behind Pfizer’s COVID-19 shot, but its original mission always revolved around oncology. With the recent success of its next-generation antibody-drug conjugate (ADC) trastuzumab pamirtecan (DB-1303, also known as BNT323) in a Phase 3 breast cancer trial, the German biotech firm appears to be stepping confidently into the cancer therapy spotlight.

The milestone announcement came on September 5, 2025, when BioNTech and its Chinese partner Duality Biologics reported that DB-1303 had met its primary endpoint of progression-free survival in HER2-positive metastatic or unresectable breast cancer. This pivotal Phase 3 trial (NCT06265428), conducted across 48 sites in China, compared DB-1303 to the existing HER2 ADC standard, trastuzumab emtansine (T-DM1). The positive outcome triggered a nearly 9% surge in BioNTech’s stock price and ignited new investor optimism around its oncology roadmap.

But this win is not merely a financial blip or a single-trial victory—it marks the first time BioNTech’s cancer pipeline has delivered Phase 3 validation in a late-stage setting. For a company long seen through the lens of pandemic vaccine production, this is an unmistakable signal of its evolving core identity.

What role does oncology play in BioNTech’s long-term pipeline strategy beyond COVID-19 vaccines?

BioNTech’s origin story is deeply rooted in cancer immunotherapy. Before the pandemic thrust it into the global limelight, the company had been steadily developing personalized mRNA cancer vaccines, immune checkpoint inhibitors, and CAR-T cell therapies. Its co-founders, Dr. Ugur Sahin and Dr. Özlem Türeci, are oncologists by training, and their vision for BioNTech was always to create highly targeted, individualized treatments for cancer.

The pivot to oncology is not a shift—it’s a return. While the COVID-19 vaccine generated billions in revenue and accelerated BioNTech’s manufacturing and regulatory capabilities, it also temporarily paused or slowed progress on several cancer-focused programs. Now, with DB-1303 delivering positive Phase 3 results and other oncology candidates progressing through the pipeline, BioNTech is reaffirming its long-term R&D focus: a multi-platform, multi-modality oncology powerhouse.

The company is now deploying resources across a diverse portfolio that includes ADCs, mRNA-based cancer vaccines, T-cell therapies, bispecific antibodies, and immune checkpoint agonists. These platforms are not siloed; they are designed to be modular and combinatorial, allowing for cross-modal treatment strategies that adapt to tumor complexity and patient-specific immune profiles.

How does the DualityBio partnership and DB-1303 differentiate BioNTech’s approach in the ADC race?

Trastuzumab pamirtecan (DB-1303) is a third-generation HER2-targeting ADC that uses a topoisomerase-1 inhibitor payload and is built on DualityBio’s proprietary DITAC (Duality Immune Toxin Antibody Conjugates) platform. It represents BioNTech’s first major foray into antibody-drug conjugates, a modality historically dominated by Seagen, Daiichi Sankyo, and AstraZeneca.

The DB-1303 molecule showed strong efficacy in preclinical models across both HER2-positive and HER2-low solid tumors. Its design potentially expands the therapeutic window while maintaining a manageable safety profile. With activity observed in breast and endometrial cancers, the candidate stands out for its flexibility across HER2 expression levels.

BioNTech and DualityBio began their strategic collaboration in April 2023. Under the agreement, BioNTech retains global rights outside of mainland China, Hong Kong, and Macau, while DualityBio oversees commercialization within those territories. The collaboration has already launched a second global Phase 3 trial—DYNASTY-Breast02 (NCT06018337)—targeting hormone receptor-positive, HER2-low metastatic breast cancer, an underserved subset of patients.

This positioning puts BioNTech in direct competition with AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan), currently the leading HER2 ADC on the global market. DB-1303’s success signals that BioNTech could mount a credible challenge to Enhertu’s dominance, particularly if the candidate continues to deliver favorable safety and efficacy results in broader tumor indications.

What other moves has BioNTech made to signal a sustained push into oncology beyond ADCs?

The success of DB-1303 is just one piece of a much larger oncology puzzle. In June 2025, BioNTech announced a $1.25 billion all-stock acquisition of CureVac, another mRNA pioneer. The move brought additional capabilities in mRNA-based cancer immunotherapy and reinforced BioNTech’s pipeline of individualized neoantigen vaccines. The CureVac deal was widely interpreted by analysts as a vertical integration play, consolidating platform innovation and reducing dependency on external partners for nucleic acid-based modalities.

Around the same time, BioNTech entered into a partnership with Bristol Myers Squibb (BMS) valued at up to $11 billion. The agreement includes co-development of BNT327, a bispecific antibody targeting a dual checkpoint axis, and builds on both firms’ shared interest in immuno-oncology. For BioNTech, this alliance strengthens its credibility among legacy pharma players and opens access to BMS’s expansive clinical and commercial infrastructure.

These moves are strategic and synergistic. They show that BioNTech is building a vertically integrated oncology company, one that spans early discovery to commercialization, across small molecules, biologics, and mRNA-based products. This depth and breadth place it in rare company alongside firms like Moderna, Gilead, and Roche in the oncology innovation race.

How are investors responding to BioNTech’s oncology pivot—and what are they watching for next?

Following the DB-1303 news, BioNTech shares jumped 8.66% on the NASDAQ to close at $112.46 on September 5, 2025. This was the stock’s largest single-day gain in months and brought its market capitalization closer to its 52-week high of $131.49. While pandemic-era highs may be difficult to reclaim in the short term, institutional sentiment has clearly shifted from “vaccine fatigue” to cautious optimism about the company’s oncology pipeline.

Analysts are particularly interested in upcoming overall survival data from the NCT06265428 trial and interim readouts from DYNASTY-Breast02. Additionally, maturing data from BioNTech’s mRNA cancer vaccine programs, especially in combination with checkpoint inhibitors, could serve as further inflection points.

Buy-side attention is also being directed toward the company’s ability to navigate regulatory pathways outside China. A successful Biologics License Application (BLA) for DB-1303 in the United States or European Union would significantly expand its commercial reach and could trigger milestone payments or partnership expansions.

There’s also growing interest in BioNTech’s manufacturing scalability and how it leverages its mRNA production experience to support oncology pipelines. The ability to produce individualized mRNA vaccines at scale—especially in regions like Europe, the U.S., and potentially Africa via its modular BioNTainers—could prove to be a key competitive advantage.

Can BioNTech sustain its oncology momentum and emerge as a long-term sector leader?

The DB-1303 Phase 3 win represents more than a trial success; it symbolizes BioNTech’s successful repositioning as a multi-modality oncology company. With a pipeline that includes everything from personalized mRNA cancer vaccines and checkpoint inhibitors to CAR-T and ADCs, the German biotech firm is now well-positioned to become a long-term player in cancer care.

The next 12 to 18 months will be critical in determining whether BioNTech’s oncology bets pay off. Success hinges not only on clinical results but also on regulatory agility, commercial execution, and continued innovation across its platforms.

If it can deliver on those fronts, BioNTech may finally—and permanently—step out of the shadow of COVID-19 and into the limelight as a global oncology leader.