Submission follows positive results from Phase III TULIP® trial
Next-Generation HER2-ADC Utilizes Byondis Technologies Aimed at Improving Treatment Outcomes
NIJMEGEN, Netherlands, July 18, 2022 /PRNewswire/ — Byondis BV, an independent Dutch clinical-stage biopharmaceutical company that creates precision medicines, today announced that the European Medicines Agency (EMA) has cleared the Marketing Authorization Application (MAA) for the company’s next-generation investigational anti-HER2 antibody. conjugate drug (ADC) trastuzumab duocarmazine (SYD985) in patients with unresectable HER2-positive locally advanced or metastatic breast cancer.
If granted, marketing authorization applies to all EU member states, as well as countries in the European Economic Area (EEA). Iceland, Liechtenstein and Norway. SYD985 will be marketed by medac GmbH, marketing partner and marketing authorization applicant of Byondis, a private pharmaceutical company based in Germany. medac holds an exclusive license to market SYD985 in all approved indications in the EU, UK and other European countries, including Iceland, Liechtenstein, Norway and Swiss.
“The approval of the MA is an important step in our mission to give hope to patients,” said the CEO of Byondis. Marco TimmersPh.D. “About one in five breast cancers is HER2-positive, often resulting in more aggressive disease. There is an urgent need to provide an alternative treatment option to these patients.”
“medac shares Byondis’ passion for providing tolerable and more effective cancer treatment options,” said Jörg Hans, medac Managing Director and CEO. “This milestone brings us closer to achieving that goal.”
The marketing authorization is supported by data from Byondis’ pivotal, multicenter, open-label, randomized Phase III clinical trial TULIP® comparing SYD985 to treatment of physician’s choice (PC) in patients with HER2- unresectable positive locally advanced or pretreated metastatic (SYD985.002/NCT03262935). The study, whose 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 compared to PC. TULIP also demonstrated favorable results in terms of overall survival (OS).
This is the second regulatory submission for Byondis’ main SYD985 program. The therapy is currently under review by the US Food & Drug Administration (FDA). The FDA granted Expedited Processing Designation in January 2018 based on promising Phase I data involving heavily pretreated late HER2-positive MBC patients (SYD985.001/NCT02277717). Byondis is also preparing the submission of the medac dossier SYD985 for the UK Medicines and Healthcare Products Regulatory Agency (MHRA).
Trastuzumab Duocarmazine (SYD985), a next-generation antibody-drug conjugate
Trastuzumab duocarmazine (SYD985) incorporates Byondis’ proprietary and proprietary duocarmazine linker-drug (LD) ByonZine® technology. The ADC is made up of the anti-HER2 monoclonal antibody trastuzumab and a cleavable linker drug called valine-citrulline-dry-DUocarmycin-hydroxybenzamide-azaindole (vc-dry-DUBA).
The antibody portion of trastuzumab duocarmazine binds to HER2 on the cancer cell surface 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’ exclusive proprietary drug-binding technology
While previous-generation ADCs improved cell targeting and killing, they were unstable in the bloodstream, leading to premature release of cytotoxic payload, affecting healthy tissue, and narrowing the therapeutic window. Byondis’ next-generation ADCs are highly stable in circulation and carry a complex, inactivated, and potent cytotoxic drug that rapidly self-destructs if released prematurely, limiting damage to healthy tissue and improving the therapeutic window.
Byondis differentiated binding drug, vc-dry-DUBA, owes its potent antitumor activity to a synthetic cytotoxin based on duocarmycin. Duocarmycins, first isolated from Streptomyces bacteria in the 1970s, bind to the minor groove of DNA and disrupt nucleic acid architecture, ultimately leading to tumor cell death.
The distinctive design of the selectively cleavable linker linking the antibody to the drug duocarmycin leads to high stability in circulation and induces efficient delivery of the cytotoxin into the tumor. Uptake of the activated payload by neighboring tumor cells with lower HER2 expression can enhance the potential for efficacy, the so-called proximity effect.
Committed to improving the lives of patients, Byondis is an independent, privately held Dutch clinical-stage biopharmaceutical company that creates innovative precision medicines targeting incurable cancers and autoimmune diseases. The company develops next-generation antibody-drug conjugates (ADCs) using its proprietary molecular concepts such as ByonZine®, its duocarmazine (LD) binding technology and ByonShieLD®, its site-specific conjugation technology. It also creates monoclonal antibodies (mAbs) and new chemical entities (NCEs) that can stand alone or be incorporated into its ADCs.
Byondis’ extensive development portfolio includes preclinical development programs as well as early and late-stage clinical development programs. The company has a dedicated team of approximately 400 employees, including highly skilled scientists and skilled technicians working in state-of-the-art, Good Manufacturing Practice (GMP) production and conjugation facilities on its campus. from Nijmegen, the Netherlands. Byondis regularly collaborates with leading global biotech and pharmaceutical companies, as well as numerous academic research institutes. For more information, visit https://www.byondis.com/.
About medac GmbH
medac GmbH is a privately held global pharmaceutical company with growing pharmaceutical and diagnostics businesses. Since its foundation in Germany in 1970, medac specializes in the treatment of diseases in the areas of indication oncology, hematology, urology and autoimmune diseases. medac is committed to improving existing therapeutic products and developing new ones, always with an emphasis on improving the quality of life of patients. medac has become known for the development of innovative products also in less common indications. This dedication has translated into a comprehensive portfolio of pharmaceutical products that help make a difference in the lives of patients. medac continuously invests in the development and manufacturing of its products as well as in its logistics capabilities to meet both the needs of patients and the demands of healthcare professionals. For more information, visit https://international.medac.de/home/.