Prof. Ugur Sahin, MD, BioNTech CEO and Co-Founder

BioNTech will expand its pipeline into antibody-drug conjugates (ADCs) and deepen its presence in oncology through an up-to-$1.67 billion collaboration with Duality Biologics (DualityBio), the companies said today.

Through the collaboration, BioNTech has licensed rights for two ADC candidates designed to fight solid tumors in DualityBio’s pipeline—its lead candidate, the Phase II DB-1303; and the preclinical-phase DB-1311. Both are topoisomerase-1 inhibitors, with DB-1303 disclosed as targeting Human Epidermal Growth Factor Receptor 2 (HER2).

DB-1303 is a third generation HER2 ADC molecule created through DualityBio’s Duality Immune Toxin Antibody Conjugates (DITAC) platform. DB-1303 has shown what the companies say is potent antitumor activity in both HER2 positive and HER2 low tumor model, with a favorable safety profile and a potentially expanded therapeutic window.

DB-1303—which has received the FDA’s Fast Track designation—is under study in the Phase II portion of a dose-escalation and dose-expansion Phase I/IIa trial (NCT05150691) designed to assess its safety and tolerability in patients with advanced solid tumors that express HER2. The estimated primary completion date for that study is June 2025.

DB-1311 is an ADC comprised of a humanized antibody and DualityBio’s proprietary DITAC linker-payload. It has exhibited potent antitumor activity in a range of tumor models representing multiple cancer types and has been well tolerated in preclinical studies,

BioNTech has inked exclusive license and collaboration agreements to develop, manufacture and commercialize the two candidates worldwide except in Mainland China, Hong Kong, and Macau, where Shanghai-based DualityBio will retain rights.

However, the agreement for DB-1311 also grants DualityBio the right to exercise a co-development cost and profit/loss sharing option, as well as a co-promotion option, for the U.S. market.

“Over the last years, the ADC field has made significant progress, overcoming several limitations and demonstrating its potential as a broadly applicable precision medicine drug class that might be an alternative to standard chemotherapy,” Prof. Ugur Sahin, MD, BioNTech CEO and Co-Founder, said in a statement. “The addition of these two ADCs to our portfolio strengthens our pipeline of immunotherapies and expands our capabilities with the aim to provide therapeutic benefits for patients with a range of solid tumors, along the entire patient journey.”

Beyond mRNA, COVID-19

BioNTech’s 38-program pipeline is now dominated by some two dozen programs of its messenger RNA-based candidates, the best known of which is its COVID-19 vaccine BNT162b2, co-developed with Pfizer. The original vaccine received FDA emergency approval in 2020, before winning full agency approval a year later, and has since been incorporated into two bivalent treatments for variants of the virus.

John Zhu, PhD, DualityBio’s founder and CEO

BioNTech has told investors it sees “growth potential for COVID-19 franchise from 2025” as it shifts its market focus from government to commercial avenues, and as it potentially introduces next-generation vaccines and novel combinations by then.

Over the past year, however, sales of the COVID-19 vaccine—BioNTech’s sole marketed product—have fallen off with demand. BioNTech finished 2022 with €17.611 billion ($19.173 billion) commercial revenues, down 7% from €18.977 billion ($20.656 billion). Worse for BioNTech, the company has issued investor guidance estimating it will only generate €5 billion ($5.442 billion) in COVID-19 vaccine revenue this year.

Cancer indications account for 24 of the 38 programs listed on BioNTech’s pipeline. BioNTech has applied its mRNA technology to develop a personalized cancer vaccine. Last year the company reported positive follow-up Phase I/II data for its wholly-owned novel chimeric antigen receptor T-cell therapy (CAR-T) candidate BNT211 in patients with relapsed or refractory advanced solid tumors—but saw no corresponding rise in its stock as a result.

BNT211 is being studied alone and in combination with a CAR-T cell Amplifying RNA Vaccine (CARVac) encoding CLDN6. The CARVac is intended to drive in vivo expansion of transferred CAR-T cells to increase their persistence and efficacy. Later this year, BioNTech has said, it expects to provide a data update on an ongoing Phase I/II dose escalation and expansion study evaluating CLDN6 CAR-T cells with or without CLDN6 CARVac in patients with CLDN6-positive relapsed or refractory advanced solid tumors.

In 2024, BioNTech expects to begin a Phase II study of BNT211 in patients with second-line plus platinum resistant testicular cancer.

BioNTech has agreed to pay DualityBio $170 million upfront and up to $1.5 billion in payments tied to achieving development, regulatory, and commercial milestones. DualityBio will also be eligible to receive single-digit to double-digit tiered royalties on net sales for both ADCs.

“This is a recognition of not only DualityBio’s next-generation ADC platform, but also its internal discovery and development capabilities,” stated John Zhu, PhD, DualityBio’s founder and CEO. “With this strategic partnership, we are committed to working together to advance the development of innovative therapies for the benefit of patients worldwide.”

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