ADC Review

Early development

The name says it all. “Byondis" (pronounced ‘beyond this’), is about going beyond the standard of care to provide novel treatments with high efficacy and low systemic toxicity for patients with unmet medical needs.

Based in Nijmegen, the Netherlands, Byondis, an independent, privately held, clinical stage biopharmaceutical research and development company, started in 2012 as a biopharmaceutical subsidiary of Dutch-based generics pharmaceutical company Synthon. This subsidiary, called Synthon Biopharmaceuticals, quickly built a promising pipeline of innovative research and development programs with an aim to create innovative precision medicines targeting intractable cancers and autoimmune diseases.

From Generics to Biotech

Synthon, the parent company of Synthon Biopharmaceuticals, was founded in 1991, and under the passionate leadership of the company's co-founder, Jacques Lemmens, Ph.D., the company rapidly became a leading developer, producer and supplier of complex generics.

After Synthon became a recognized global entity, Lemmens redirected his focus -- from producing affordable versions of off-patent medicines, to creating next generation precision medicines. His dream: develop “new molecules that matter and lead to medical breakthroughs.”

In 2007, building on this Lemmens passion for innovation, Synthon started its biopharmaceutical activities, ultimately leading to the establishment of a new biopharmaceutical subsidiary. Called Synthon Biopharmaceuticals, this subsidiary quickly built a promising pipeline of innovative R&D programs designed to develop new biological entities (NBEs) and new chemical entities (NCEs) using proprietary molecular concepts.

In 2019 Synthon Biopharmaceuticals' separated from Synthon, which resulted in the formation of a new independent company, which, in 2020, was rebranded as Byondis.

Antibody-Drug Conjugates

The cornerstone of Byondis' research and development efforts are the company's next generation antibody-drug conjugates (ADCs). These targeted agents open the way for novel treatment options for patients diagnosed with cancer or hematological malignancies. These ADCs aim to target difficult-to-treat cancers with powerful cytotoxins that have a wider therapeutic window and lower systemic toxicity. They are designed to destroy cancer cells and spare normal, healthy, cells. These novel therapies are based on Byondis' distinctive, proprietary technologies, novel mechanisms of action, and selected combination strategies.

Byondis takes its innovative portfolio beyond the laboratory, from discovery to clinical drug development, up to and including pivotal clinical studies. This relies on an up-to-date pipeline of new biological and chemical entities.

Byondis CEO Marco Timmers, Ph.D. explained: “We employ the latest insights in tumor biology and patient unmet needs in our search for and development of new mechanisms and new targets for monoclonal antibodies, ADCs and small molecule programs. Our aim is to have a solid pipeline with programs at different development stages.”

Using this approach, Byondis has a broad development pipeline built on proprietary technologies, with preclinical as well as early- and late-stage clinical development programs.

This pipeline reflects the company's expertise in research, lead identification, preclinical/clinical development, process development and manufacturing.

The company's lead program is [vic-]trastuzumab duocarmazine (SYD985), an antibody-drug conjugate (ADC) currently under U.S. and European regulatory review. ADC Drug Map Link

Creating Precision Medicines

With a dedicated team of about 400 employees, including highly educated scientists and skilled technicians working in state-of-the-art Research & Development and Good Manufacturing Practice (GMP) production facilities on its Nijmegen campus in the Netherlands, Byondis creates both targeted and immuno-oncology [IO] therapies.

Byondis four-phased value creation strategy:

• Following positive results of the pivotal Phase III TULIP® study (NCT03262935) investigating [vic-]trastuzumab duocarmazine (SYD985) in HER2-positive metastatic breast cancer, Byondis submitted a Biologics License Application (BLA) to the U.S. Food & Drug Administration (FDA) and a Marketing Authorization Application to the European Medicines Agency (EMA). The company has also entered into a License and Collaboration Agreement and a Supply Agreement with Germany-based medac a privately held, global pharmaceutical company originally founded in 1970, to commercialize SYD985 in Europe and the United Kingdom, pending regulatory approvals. [Vic-]trastuzumab duocarmazine (SYD985) was developed using Byondis, ByonZine® and ByonNative® technologies. ADC Drug Map Link

• The potential of SYD985 in other clinical indications is being explored. A Phase II trial is evaluating the safety and efficacy of SYD985 as a standalone therapy in HER2-expressing metastatic endometrial (uterine serous) cancers. ADC Drug Map Link

• New programs to enter clinical development, with preclinical data suggesting a promising therapeutic window in patients:
  • BYON3521. This ADC just entered the clinic, and is designed to target c-Met, which is widely over-expressed in various solid tumors. Developed with Byondis ByonZine® and ByonShieLD® technology, this agent is currently in preclinical development. ADC Drug Map Link
    
    
  • BYON4228, this antibody (mAb) is the lead cancer immunotherapy from Byondis’ next generation IO program. The mAb targets SIRPα, which increases the tumour-killing capacity of the immune system.
  
  
  • BYON4413 is an ADC directed against the molecular target CD123 (interleukin-3 receptor alpha chain), which is expressed in many hemato-oncological malignancies. Developed with Byondis ByonZine® and ByonShieLD® technologies, this investigational agent is currently in preclinical development. ADC Drug Map Link

The company continues to identify research programs ensuring a sustainable R&D pipeline in the coming decade. In its early discovery pipeline, three new platforms were identified, including:

• A novel linker-drug technology to generate IO ADCs.
• A linker-drug technology to generate ADCs with potential in both oncologic and other indications, such as autoimmune diseases
• A platform to increase the tumour-specificity of mAbs and ADCs.

Collaborative Research

Byondis regularly collaborates with leading global biotechnology and pharmaceutical companies, as well as many academic research institutions. While uniquely positioned to take its innovative portfolio beyond the laboratory, up to and including pivotal clinical studies, the company welcomes partners and collaborators to help speed its medicines to those who need them.

The ultimate goal: Making Hope Real for patients with a current unmet medical need.

Key technologies

ByonZine®

Duocarmazine Linker-Drug Technology and cleavable DNA-damaging linker-drug. ADCs developed using this proprietary technology can effectively eliminate heterogeneous tumors via the unique target-mediated and bystander mechanisms of action and kills both dividing and non-dividing cancer cells with extremely low levels of free drug in circulation.

ByonNative®

A differentiated antibody conjugation platform which allows ADC generation via partially reduced native disulfide bonds. This is a proprietary process that removes unwanted non-conjugated and over-conjugated species and enables fast generation of ByonZine® ADCs with antibodies of interest.

ByonShieLD®

A site-specific antibody conjugation platform designed to create uniform ByonZine® ADCs via orthogonal cysteine activation and conjugation technology. Using a controlled method of connecting the linker-drug to the antibody, this technology shields the hydrophobic payload and creates ADCs with a superior therapeutic index and excellent manufacturability.

ByonFoLD®

A dual linker-drug antibody conjugation platform designed to create well defined two-in-one ADCs in which two different payloads are conjugated in a compatible fashion to a single antibody. This technology allows the creation of next-generation ADCs with synergistically operating dual payloads.

ByonBranch®

A branched linker technology. Branched linker technology allows the coupling of payloads to an antibody that results in ADCs with reduced hydrophobicity.