German-based BioNTech and Duality Biologics (Suzhou) Co, a Shanghai-based clinical-stage biotech company, have entered into exclusive license and collaboration agreements for the ongoing development manufacture and globally* commercialize two investigational antibody-drug conjugates (DB-1303, also known as BNT323, and DB-1311) directed against HER2.

Anti-HER2 therapy has recently emerged as an effective targeted treatment approach for patients diagnosed with advanced and recurrent HER2 positive and HER2 low tumors, resulting in significantly prolonged progression-free and overall survival when combined with chemotherapy.[1].

The collaboration between DualityBio and BioNTech comes at the time that the COVID-19 pandemic enterers a new phase. By adding the investigational agents, ADCs will become an additional, investigational drug class in BioNTech’s oncology portfolio, which already includes an anti-CTLA-4 antibody BNT316 (ONC-392; developed in collaboration with OncoC4) for the treatment patients diagnosed with NSCLC who progress after treatment with a PD-1/PD-L1 and a CAR T-cell therapy candidate BNT211.

As part of the collaboration, BioNTech will gain access to DualityBio’s lead candidate, DB-1303, a third generation Human Epidermal Growth Factor Receptor 2 (HER2-) targeting ADC based on the company’s’ proprietary Duality Immune Toxin Antibody Conjugates (DITAC) platform. The investigational agent is a topoisomerase-1 inhibitor-based ADC directed against HER2.

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In preclinical development DB-1303 exhibited potent anti tumor activity in both HER2 positive and HER2 low tumor models with a favorable safety profile and a potentially expanded therapeutic window.

Both preclinical data and preliminary clinical data from DB-1303 suggest the potential of DB-1303 to address unmet medical needs in various HER2 expressing cancers.

DB-1303 received the Fast Track designation from the U.S. Food and Drug Administration and is currently in a Phase 2 clinical trial (NCT05150691) for HER2-expressing advanced solid tumors.

BioNTech will also gain access to a second topoisomerase-1 inhibitor-based ADC candidate, DB-1311, an investigational agent comprised of a humanized antibody and DualityBio’s proprietary DITAC linker-payload. In preclinical development DB-1311 exhibited potent antitumor activity in a range of tumor models representing multiple cancer types and has been well tolerated in preclinical studies, with a good pharmacokinetics profile. The wide therapeutic window demonstrated by preclinical antitumor activity and its safety profile support the potential of DB-1311 to address unmet medical needs across a broad range of cancers.

Significant progress
“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,” said Prof. Ugur Sahin, M.D., Chief Executive Officer and Co-Founder of BioNTech.

“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.”

“We are delighted to partner with BioNTech, a leading company which brings transformational medicine to patients through innovation,” noted  John Zhu, Ph.D., Founder and CEO of DualityBio.

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

Under the terms of the agreements, DualityBio will receive upfront payments for both asset licenses totaling $170 million, and additional development, regulatory and commercial milestone payments for both assets, potentially totaling over $1.5 billion.

DualityBio will be eligible to receive single-digit to double-digit tiered royalties on net sales for both ADC assets. BioNTech will hold global commercial rights, while DualityBio will retain commercial rights for Mainland China, Hong Kong Special Administrative Region and Macau Special Administrative Region.

As part of the agreement for DB-1311, DualityBio has the right to exercise a co-development cost and profit/loss sharing option for DB-1311 for the U.S. market, as well as a co-promotion option for the U.S. market.page1image1765708448

Note: * Excluding Mainland China, Hong Kong Special Administrative Region and Macau Special Administrative Region.

Clinical trials
A Study of DB-1303 in Advanced/Metastatic Solid Tumors – NCT05150691

[1] Buza N. HER2 Testing and Reporting in Endometrial Serous Carcinoma: Practical Recommendations for HER2 Immunohistochemistry and Fluorescent In Situ Hybridization: Proceedings of the ISGyP Companion Society Session at the 2020 USCAP Annual Meeting. Int J Gynecol Pathol. 2021 Jan;40(1):17-23. doi: 10.1097/PGP.0000000000000711. PMID: 33290351.

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