EMA Validates Marketing Authorization Application for Trastuzumab Duocarmazine (SYD985) in HER2-Positive Metastatic Breast Cancer

Submission Follows Positive Results of Phase III TULIP® Trial

Next Generation HER2-ADC Uses Byondis Technologies Aimed at Improving Treatment Outcomes

NIJMEGEN, Netherlands, July 18, 2022 /PRNewswire/ -- Byondis B.V., an independent, Dutch clinical stage biopharmaceutical company creating precision medicines, announced today that the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for the company's investigational next generation anti-HER2 antibody-drug conjugate (ADC) trastuzumab duocarmazine (SYD985) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer (MBC).

If granted, the marketing authorization applies to all EU member states, as well the European Economic Area (EEA) countries Iceland, Liechtenstein and Norway. SYD985 will be marketed by Byondis' commercialization partner and marketing authorization applicant medac GmbH, a privately owned pharmaceutical company based in Germany. medac has an exclusive license to market SYD985 in all approved indications in the EU, UK and other European countries, including Iceland, Liechtenstein, Norway and Switzerland.

"The MAA validation is an important step forward in our mission to make hope real for patients," said Byondis CEO Marco Timmers, Ph.D. "About one in five breast cancers are HER2-positive, often resulting in a more aggressive disease. There is a dire need to provide an alternative treatment option to these patients."

"medac shares Byondis' passion for delivering tolerable, more effective cancer treatment options," said medac Managing Director, CEO Jörg Hans. "This important milestone brings us closer to realizing this goal."

The MAA is supported by data from Byondis' pivotal Phase III TULIP® multi-center, open-label, randomized clinical trial comparing SYD985 to physician's choice (PC) treatment in patients with pre-treated HER2-positive unresectable locally advanced or metastatic breast cancer (SYD985.002/NCT03262935). The study, of which the preliminary results were presented at the 2021 ESMO Congress, met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement of 2.1 months over PC. TULIP also demonstrated supportive overall survival (OS) results.

This is the second regulatory submission for Byondis' lead program SYD985. The therapy is currently under review by the U.S. Food & Drug Administration (FDA). The FDA granted the therapy fast track designation in January 2018 based on promising Phase I data involving heavily pre-treated last-line HER2-positive MBC patients (SYD985.001/NCT02277717). Byondis is also preparing the medac SYD985 dossier submission for the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Trastuzumab Duocarmazine (SYD985), a Next Generation Antibody-Drug Conjugate

Trastuzumab duocarmazine (SYD985) incorporates Byondis' distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine®. The ADC is comprised of the anti-HER2 monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA).

The antibody part of trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell and the ADC is internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 is considered a form of targeted therapy.

ByonZine®, Byondis' Distinctive, Proprietary Linker-Drug Technology

While earlier generation ADCs improved targeting and cell killing, they were unstable in the bloodstream, leading to premature release of the cytotoxic payload, impacting healthy tissue and narrowing the therapeutic window. Byondis' next generation ADCs are highly stable in circulation and carry an intricate, inactivated and potent cytotoxic drug that rapidly self-destructs if it is prematurely released, limiting damage to healthy tissue and improving the therapeutic window.

Byondis' differentiated linker-drug, vc-seco-DUBA, owes its potent antitumor activity to a synthetic duocarmycin-based cytotoxin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt the nucleic acid architecture, which eventually leads to tumor cell death.

The distinctive design of the selectively cleavable linker connecting the antibody to the duocarmycin drug leads to high stability in circulation and induces efficient release of the cytotoxin in the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression may improve the efficacy potential, the so-called bystander effect.

About Byondis

Driven to improve patients' lives, Byondis is an independent, privately held, Dutch clinical stage biopharmaceutical company creating innovative precision medicines targeting intractable cancers and autoimmune diseases. The company is developing next generation antibody-drug conjugates (ADCs) using its proprietary molecular concepts such as ByonZine®, its duocarmazine linker-drug (LD) technology, and ByonShieLD®, its site-specific conjugation technology. It is also creating monoclonal antibodies (mAbs) and new chemical entities (NCEs) that can stand alone or be incorporated in its ADCs.

Byondis' broad development portfolio comprises preclinical as well as early- and late-stage clinical development programs. The company has a dedicated team of about 400 employees, including highly educated scientists and skilled technicians working in state-of-the-art R&D and Good Manufacturing Practice (GMP) production and conjugation facilities on its campus in Nijmegen, the Netherlands. Byondis regularly collaborates with leading global biotechnology and pharmaceutical companies, as well as many academic research institutions. For more information, visit https://www.byondis.com/.

About medac GmbH

medac GmbH is a privately held, global pharmaceutical company with a growing pharmaceutical and diagnostics business. Since its foundation in Germany in 1970, medac has been specializing in the treatment of diseases within the indication areas oncology, hematology, urology and autoimmune disorders. medac is committed to the refinement of existing and the development of new therapeutic products – always with the focus on improving patients' quality of life. medac has become known for developing innovative products also in less common indications. This dedication has resulted in a comprehensive portfolio of pharmaceutical products that help make a difference in the lives of patients. medac continually invests in its product development and manufacturing as well as logistic capacities to meet both patients' needs and the demands of healthcare professionals. For more information visit https://international.medac.de/home/.

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