Rebekka: “It is a biomarker for bone marrow fibrosis in patients with a type of blood cancer called ‘myeloproliferative neoplasm’ (MPN). The first phase of MPN is associated with a relatively high quality of life. However, patients may progress to a second phase which is characterized by fibrosis of the bone marrow. The patients’ life expectancies drop dramatically from more than 15 years to one and a half years as soon as bone marrow fibrosis develops. At present, there are two problems in the clinical management of MPN. First, there is no biomarker to identify early signs of fibrosis. Second, there is no satisfactory therapy to interfere with the fibrosis. We have identified a molecule in the blood called ‘alarmin heterodimer S100A8/S100A9’ that may solve both problems because it is a targetable biomarker. It may act as a predictive biomarker and a novel therapeutic target in one.” 

Jan: “The strength of this project is that it clearly responds to an unmet need. Right now, the only curative option for patients with MPN is allogeneic stem cell transplantation. However, the majority of patients are not eligible for this challenging procedure. In addition, there are two approved drugs for the treatment of MPN, but neither are curative and both have severe side effects. And none of the available treatments address the fibrosis, which is the life-threatening factor in these patients. From a business point of view, this means that there are no competitors.” 

Rebekka: “Yes, and we have also identified an existing experimental drug that acts on the alarmin biomarker. This drug has reached Phase 3 of the clinical studies in prostate cancer patients. It showed favourable pharmaceutical properties, but did not improve survival. So, its development for prostate cancer was discontinued by the company. We have targeted the alarmin biomarker with this drug in a mouse model, and it completely ameliorated fibrosis and reduced the cancer cell burden. So, I have great expectations for this biomarker in combination with this repurposed drug.” 

Jan Groen - CEO at Intravacc and member of the Investment Advisory Committee of the Oncode Bridge Fund

Jan: “The Oncode Bridge Fund receives many investment propositions. I was approached by Oncode in 2019 to help judge these proposals together with two other advisors. We evaluate whether the proposals are innovative and we consider the market size. We also consider the position of the product compared to existing products. That means we look at it not only from a clinical point of view, but also regarding the reimbursement options in the Netherlands and abroad. In fact, many new discoveries result in higher costs rather than a cost reduction. These aspects need to be considered before one decides to invest in something.” 
 
Rebekka: “This is exactly my weakness as an academic researcher: these health economic considerations are completely new to me. In the grant proposal, we also had to discuss the commercial aspects. I could not have written that part without the help of the Oncode Valorization Team. They are specialized in valorization in the field of oncology and they have many contacts. I have a specific go-to person in the team. I contacted her and she helped me make a convincing case by setting up discussions with clinicians and pharmaceutical companies, and by performing market research. This initial research showed that the biomarker combined with a therapeutic target has high commercial potential.” 

Jan: “For diagnostic tests in general, the added value for patients should be extremely clear. So, for instance: can cancer be detected at an earlier stage or can the test result guide treatment options? And how does the product compare to existing procedures and tests? It may be quite difficult to develop a biomarker per se because biomarkers are not easy to patent.” 
 
Rebekka: “Indeed, I learnt that investors are usually not interested in biomarkers per se. But an actionable biomarker is very attractive. The focus of our business case is that we discovered a novel therapeutic target which also acts as biomarker to identify patients that would benefit from treatment. If the biomarker goes up, treatment with an inhibitor targeting the biomarker can start. We have already filed a patent application for targeting alarmins and using this drug in patients with MPN and bone marrow fibrosis.” 

Rebekka Schneider - Associate Professor of Medicine at Erasmus MC and Oncode Investigator

Rebekka: “We will first team up with clinical study groups to validate the alarmin biomarker in a larger group of patients. Next, we will prepare a Phase 1b/2 clinical study of the drug as a treatment. We hope to deliver the proof-of-concept needed to enter into license deals with companies. We will also consider commercializing the targetable biomarker through other avenues, for example through a start-up company. The advantage of coordinating a start-up myself is that it will be in my own hands. I think this will speed up the process because I will act as an advocate for the product.” 

Jan: “This is an important yet difficult decision. Many scientists do not have the skills required to run a business. They find it hard to make the switch from science to business and do not have the vision and insight required to scale up and attract investors. In addition, scientists tend to be interested in everything. So, they will easily start pursuing side tracks and end up doing sixty different projects, losing focus on the end product. Problems often arise after two or three years, because the roles of CEO and CTO get mixed up. It is good to have somebody in charge that understands the science behind the innovation, especially in the start-up phase. The ideal CEO of a small biotech start-up has a scientific background, experience in starting up a business, the capacity to build bridges, and the capacity to find the right talents to bring the company to the next phase. It truly is an art to recruit additional funding and to find investors.” 
 
Rebekka: “Yes, these are things to carefully consider indeed. Industry is already interested in our developments. We can offer companies a de-risked new use for this drug and associated intellectual property, access to the necessary patient cohorts for clinical trials and market exclusivity. We expect this drug for MPN to be eligible for orphan drug designation. To cover costs for the clinical studies to follow the ERC project, we will apply for additional funding from various sources. Oncode Valorization team is helping me with that as well. It has always been my dream to translate our findings into an actual patient setting, and I am learning a lot on this journey towards clinical application.” 

Credits: interview by Linda van den Berg; photography by Marloes Verweij, Laloes Fotografie