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The latest Byondis investigative therapy that will soon enter Phase I or First-in-Human (FiH) study is also the company’s first immuno-oncology (IO) therapeutic, BYON4228. How and why it got there is the stuff that researchers’ dreams are made of.

BYON4228 is a monoclonal antibody (mAb). A mAb is – per the US National Cancer Institute (NCI), “a type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the surface of cancer cells.” Monoclonal antibodies can be used to diagnose and treat many diseases, such as cancers. They can be used alone or to carry drugs, toxins, or radioactive substances directly to cancer cells.[1]

About 19 years ago, Timo van den Berg, Ph.D., now Byondis Senior Director, Immuno-Oncology, was researching immune system receptors first at the Vrije Universiteit (VU) Amsterdam and later at Sanquin Research in Amsterdam. One of them was SIRPα. New information had just come out about the possibility that SIRPα, in combination with CD47, could form an ‘immune pathway’ in oncology, in other words, a way to fight cancer via the power of the immune system (#ThePowerofIO). This led to the discovery of the CD47-SIRPα axis as an innate immune checkpoint – a ‘don’t eat me’ signal that allows tumors to escape recognition and destruction by the immune system.

What followed was a Byondis-Sanquin partnership and the development of the anti-SIRPα mAb BYON4228. By inhibiting the CD47-SIRPα axis, BYON4228 prevents the inhibitory “don’t eat me” signal to be detected, stimulating the immune cell to do what it is supposed to do: destroy the cancer cell.

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Currently, Byondis is preparing to start a Phase I study (NCT05737628) to evaluate BYON4228 alone and in combination with another mAb, rituximab, in patients with relapsed/refractory CD20-positive B-cell non-Hodgkin’s lymphoma. A Phase I trial tests the safety, side effects, best dose, and timing of a new treatment.[2]

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Teamwork makes the dream work
Before BYON4228 made it to this milestone, it, like all investigational therapies, was put through its paces.

Step 1
The multidisciplinary Research team singles out treatments that have the best chance of succeeding and making a difference in patients’ lives. They optimize the compounds by working with different departments, such as: Medicinal & Protein Chemistry (MPC), In Vitro Pharmacology (IVP), Biomarker Discovery & Development (BDD), In Vivo Pharmacology, Toxicology & DMPK (PTD), and Bioanalysis & Protein Interaction (BAPI). Then they provide input on clinical trials, including data on, for example, pharmacodynamics (how medicines affect the body), pharmacokinetics (how the body affects medicines) and efficacy.

Step 2
The baton is passed to the Biopharmaceutical Development teams. These teams develop the processes and products in preparation for clinical trials. These multidisciplinary teams fall under two main groups – Development and GMP (Good Manufacturing Practice). They include many specialists, such as: molecular, cell and microbiologists, biochemists and analytical chemists, process engineers, and operators and analysts – complemented by the Quality Control team.

Step 3
Next, Byondis’ Clinical Research and Development teams prepare, implement and manage global clinical trials to test the safety and efficacy of the medicinal compounds in humans. As a clinical-stage biopharmaceutical company, Byondis is responsible for managing and safeguarding patient safety in its studies. This involves collecting, investigating and proactively evaluating information relating to potential side effects during the clinical trial phase. Working with CROs (Clinical Research Organizations) and the study sites’ hospital oncologists, the clinical teams review and interpret the drug safety and efficacy data.

Together, Byondis’ multidisciplinary teams come up with the best drug development strategies and do so with great insight into how the therapy works, which tumor it targets, and which patients could benefit.

Clinical trial
First-in-human Dose Escalation and Expansion Study With the SIRPα-directed Monoclonal Antibody BYON4228 – NCT05737628

Reference
[1] NCI Dictionary of Cancer Terms. National Cancer Institute. Online. Last accesses on April 29, 2023.
[2] NCI Dictionary of Cancer Terms. National Cancer Institute. Online. Last accesses on April 29, 2023.

Featured image courtesy: © 2022 – 2023 Byondis. Used with permission.

Byondis is a sponsor of ADC Review | Journal of Antibody-drug Conjugates and Onco’Zine.

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Marco Timmers, Ph.D.
Marco Timmers is Chief Executive Officer at Byondis. He is an established leader with more than two decades of experience in pharmaceutical research and development and an extensive network spanning both industry and academia. Prior to his appointment as Byondis CEO, Timmers held the position of Chief Scientific Officer of Synthon Biopharmaceuticals (which later became Byondis) since it became a Synthon subsidiary in 2012. In this role, he was responsible for the development of a pipeline of new biological and chemical molecular entities, including monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and small molecules. Before joining Synthon Biopharmaceuticals, Timmers worked for more than 15 years at Organon, Schering-Plough and MSD. During this period, he held positions of increasing responsibility, ultimately serving as Head of Pharmacology and Site Lead for Women’s Health and Endocrinology and as a member of the R&D and Site Management teams. Timmers holds an MSc in Chemistry and a PhD in Bioorganic Chemistry, both from Leiden University, the Netherlands.
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Timo K. Van den Berg, Ph.D.
Timo K. van den Berg as senior director, Immuno-Oncology (IO) Research and Development at Byondis. He is is instrumental in helping shape Byondis’ IO pipeline, which includes the anti-SIRPα monoclonal antibody BYON4228. As a longstanding Byondis collaborator, Professor van den Berg played a pivotal role in the discovery of the CD47-SIRPα axis as an innate immune checkpoint. CD47 is known in the IO space as the “don’t eat me” signal that allows tumors to escape recognition and destruction. Van den Berg brings to Byondis more than 30 years of experience in the IO field -- as a renowned researcher, educator, inventor, lecturer and coauthor of over 175 peer-reviewed publications. His most recent position was head and principal investigator, Immunotherapy Laboratory, Department of Molecular Hematology at Sanquin Research, Amsterdam, the Netherlands. Since 2017, Van den Berg has been professor of Immunotherapy, Vrije Universiteit, which is affiliated with the Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Center. He spent 25 years as research group leader and department head at Amsterdam University Medical Center and Sanquin Research. Sanquin, a non-profit organization responsible for the blood supply in the Netherlands, also develops and produces pharmaceutical products, conducts scientific research and develops and performs diagnostic services. Van den Berg is a member of many boards, including Amsterdam Infection and Immunity Institute and Cancer Center Amsterdam. His professional memberships include the Dutch Society of Immunology and the European Society for Clinical Investigation. He received his Ph.D. from Amsterdam’s Vrije Universiteit (VU), and his M.Sc. in Biological Sciences (cum laude) from the University of Amsterdam (UoA)

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