Oncode has developed an overarching valorization strategy to speed up the translation of new insights in cancer biology into tangible applications for patients, society, and the oncology community. Key to Oncode’s valorization strategy are its affiliation agreements with Partner Institutes, which grant Oncode the exclusive right to manage and commercialize the intellectual property (IP) rights developed by an OI and his/her lab. This effectively means that over 900 Oncode researchers work together to execute a single strategy focused on oncology and receive proactive support to bring their discoveries/inventions to patients and society. A substantial fraction of Oncode funding (~16% for the first 5-year phase) is dedicated to the actions of the valorization team, an international team of 7 business developers, 1 fund manager, a valorization coordinator, and a data entry operator. The valorization team is the first point of contact for OIs and their research groups. As a result, Oncode’s business developers have become an integrated part of the research groups, which has the benefit that inventions are recognized earlier so that suitable valorization channels can be identified and activated swiftly. Furthermore, the availability of dedicated valorization funds enables Oncode business developers to swiftly adapt proposals and act on new opportunities. In 2021, the valorization team was very active and, as it did in 2020, surpassed the yearly targets set at the outset of Oncode. See figures below.
research related agreements in 2021
technology development projects funded in 2021
early HTA’s executed
spin-off companies with 17 FTE employed
success rate strategic funding support
new drug repurposing projects awarded in 2021
new invention disclosures in 2021
licence agreements in 2021
Impact of Technology Development fund
The Oncode Technology Development Fund (TechDev fund) was established to address scientific, technical, and business issues with the aim of increasing the likelihood that Oncode inventions can be licensed and further developed.
Achieving Proof of Concept
Oncode aims to accelerate the translation of academic research findings into better diagnostics and better treatments for cancer patients. To that end, it focuses on de-risking innovations at an early stage.
The Oncode Oncology Bridge Fund, managed by Oncode B.V., is an investment fund of €7.2M that provides pre-seed and seed capital to commercially viable enterprises originating from within the Oncode community to help translate their research ideas into market-ready investment opportunities.
Oncode Strategic funding support
Oncode’s Strategic Funding Support programme aims to help OIs navigate the funding landscape and thereby boost Oncode research funding. The programme provides tailored funding strategies for OIs and spin-off companies, offers training workshops and ‘tips & tricks’ for acquiring the most frequent types of grant, and collaborates with external parties and funding bodies on training and workshops.
Affordable Health Care programme
Oncode is dedicated to contributing to the affordability and sustainability of cancer healthcare solutions and aims to do so by leveraging its expertise and position in the valorization value chain to ensure affordability and sustainability obligations are included in applicable Oncode activities.
Valorization in person
Impact of Technology Development fund
Technology development fund 101: The Oncode Technology Development Fund (TechDev fund) was established to address scientific, technical, and business issues with the aim of increasing the likelihood that Oncode inventions can be licensed and further developed. The fund is managed by the Valorization Team and all projects are directly associated with an Oncode invention. Projects include activities such as drug target validation, high throughput screening, medicinal chemistry, toxicological studies, pK/pD studies, the formulation of drugs to support Oncode CPoC clinical trials, and health technology assessments (HTAs). With a total budget of €4M, the fund has so far funded 24 projects of which 7 were awarded in 2021. Six projects were completed in 2021. The value of the TechDev fund is particularly well illustrated by the two examples below.
Carl Figdor (Radboud UMC) - €149K, 1.5 years: OI Carl Figdor (Radboud UMC) is a renowned expert in the field of tumour immunology. His research group aims to understand the function of antigen presenting cells (APCs) as major regulators of immune response and harness their function for the development of cancer immunotherapies. Adoptive cell treatments, such as TIL or CAR-T- therapy, require T-cells from the patient to be removed, engineered ex-vivo and re-infused into the patient in order to stimulate the immune system to recognize tumour cells. While this has emerged as a powerful and potentially curative therapy for certain cancers (two CAR-T therapies entered the market after FDA approval in 2017), the approach suffers from issues. For example, it was only effective in a subset of patients, and it is an autologous therapy that has therapy-associated toxicity and high production and administrative costs. The Figdor lab at RUMC has created a modular, polymer-based, off-the-shelf antigen presenting cell that can be loaded with key signalling molecules to stimulate the immune system to generate immune cells primed against antigens of choice.
While this novel technology can be used ex-vivo as the T cell activating agent in CAR-T therapy, its real novelty lies in its ability to be administered in-vivo, eliminating the need for ex-vivo manipulation. Through Oncode’s TechDev Fund support, the Figdor lab was able to generate in-vivo proof of concept, which supported the launch of Oncode’s 7th spin-off company (Simmunext biotherapeutics) in March 2022. The company will develop a technology platform for both ex-vivo and in-vivo activation of a wide variety of tumour-reactive T cells, such as B-cells, NK cells, TILs and DCs in the fields of oncology, (auto)immune, and infectious disease.
Carl Figdor: “The Tech Dev grant has been very important for performing the experiments needed to turn our findings into a product. With its support in getting the Tech Dev grant, Oncode expedited the in vivo experiments in mice, and by that - supported me in taking the first steps towards translation into the clinic”.
Rebecca Schneider (EMC) - €95K, 1.5 years: To date, there are no effective therapy options for patients suffering from myeloproliferative neoplasms (MPNs), a rare blood cancer in which patients’ bone marrow produces excess platelets and red and white blood cells. Furthermore, no therapy is in development or has been evaluated in the clinic that clearly demonstrates the ability to target the disease-causing mutated hematopoietic stem cells. Work from the Schneider lab has shown that bone marrow stromal cells can act as protagonists of the mechanisms underlying this blood cancer type and might therefore provide a long-sought therapeutic target.
In a CPoC study (see section 3.3.2) the Schneider group is investigating the effects of a new type of small molecule drug which acts on the bone marrow stromal cells and could therefore be relevant for patients suffering from MPNs. Work in the Schneider lab has provided indications that multiple molecular pathways underlie MPNs, and pharmacologic interference in these intertwined molecular mechanisms could potentially lead to a more pronounced effect on disease progression. Within this TechDev project, Dr. Schneider will evaluate if the effects of standard-of-care treatment for MPNs can be increased when combined with this new therapy, which is currently being tested in a phase 3 clinical trials for prostate cancer. The TechDev project will be used to gain the additional data needed to gain a more solid IP position for the use of a small molecule inhibitor alongside existing therapies. Through negotiation with the industry partner currently developing the new therapy, Oncode has ensured the compound is available for use in the TechDev and CPoC projects.
Achieving Proof of Concept
Clinical proof of concept 101: Oncode aims to accelerate the translation of academic research findings into better diagnostics and better treatments for cancer patients. To that end, it focuses on de-risking innovations at an early stage. Oncode has a dedicated fund (total €10M) to invest in (pre)clinical proof-of-concept studies to demonstrate the potential diagnostic or therapeutic value of a research finding. Oncode’s team of experts provides guidance and advice to all OIs applying for Clinical Proof-of-Concept (CPoC) funding. In 2021, Oncode awarded 4 CPoC projects with a total budget of €2.8M. Out of a total of 17 awarded CPoC projects awarded by Oncode up to the end of 2021, 3 have now been completed.
To increase interaction between basic scientists and clinicians, Oncode organizes clinical workshops that aim to facilitate a dialogue about clinical challenges and how scientific insights can contribute to solving them. Due to the impact of the COVID-19 pandemic, Oncode was only able to host one of these clinical workshops in 2021, centered around melanoma. Clinician Karijn Suijkerbuijk (UMCU) and OI Sjoerd van der Burg (LUMC) hosted the workshop, which brought together 44 experts with different fields of expertise from across the Netherlands.
New project in the spotlight: Oncode is pleased that the flow of high-quality projects continues to make its way towards the clinic. In 2021, projects were awarded to Edwin Cuppen (UMC Utrecht, see below), Maarten van Lohuizen (NKI) , Rebekka Schneider (Erasmus MC) and Sjoerd van der Burg (LUMC), the last three listed being in collaboration with industry partners.
GLOW study: In 2019, Edwin Cuppen attended a clinical workshop organized by Oncode focused on gliobastoma. Recognizing the unmet clinical need for more effective treatment strategies, Cuppen quickly recognized the potential of whole genome sequencing (WGS) in helping to combat this disease. Cuppen contacted multiple clinicians to discuss the issue and eventually set up a CPoC project. The project team submitted the ‘GLOW’ (Glioblastoma targeted treatment option maximisation by WGS) study proposal, in which Cuppen together with clinicians Filip de Vos (UMC Utrecht) and Marike Broekman (Haaglanden MC) will investigate the added value of WGS on tumour tissue obtained from glioblastoma patients during routine operations for a first relapse after standard treatment with chemo and radiotherapy. The goal of the GLOW project is to find suitable treatments with targeted medication as well as additional treatment options. Funding for the project was awarded in May 2021.
Glioblastomas are the most common malignant primary brain tumours, affecting approximately 1,000 patients per year in the Netherlands. The prognosis for these patients is very unfavourable, with only ~17% of patients still alive after two years. Despite extensive research into the biology of these tumours, the standard of care has hardly changed over the past 15 years. New treatment strategies are therefore urgently needed. The aim of this project is not only to provide additional therapeutic options for patients with recurrent glioblastomas, but also to contribute new insights into the biology of these deadly tumours. The project therefore has the potential to change the standard of care for patients with glioblastoma.
Filip de Vos, MD (UMC Utrecht): “The unmet clinical need of discovering new treatments is almost palpable in operating and consulting rooms when we treat glioblastoma patients. GLOW presents a unique opportunity to examine the promise of whole genome sequencing in delivering accurate personalized treatment as an addition to expert neuro-oncology care in major Dutch centers.”
Edwin Cuppen (UMC Utrecht): “Following the Oncode glioblastoma workshop in Rotterdam, I started working with a number of clinicians to develop a clinical proof-of-concept study.”
First ‘Oncode’ therapeutic tested in patients: In 2019, Oncode awarded a grant to OI Sjoerd van der Burg, his colleague Thorbald van Hall (both LUMC), and pulmonary oncologist Joachim Aerts (Erasmus MC) to develop a potential anticancer vaccine called TEIPP (T-cell epitopes associated with impaired peptide processing) targeting immunotherapy. The project consisted of preclinical validation work, which if successful would be followed by a clinical trial. In 2021, Oncode was proud to announce that a clinical trial with the project’s newly developed vaccine against Non-Small Cell Lung Cancer (NSCLC) started at Erasmus MC.
The newly developed vaccine, which teaches the immune system of lung cancer patients to recognize and clear their own tumour cells, could offer relief to a large proportion of nearly 10,000 patients who receive a NSCLC diagnosis each year in the Netherlands. NSCLC is the most common form of lung cancer and in 80% of cases is unresponsive to existing treatments, including immunotherapy, at the time of diagnosis. Treatment options for these patients are therefore very limited. The research team led by Sjoerd van der Burg hopes to change this with an innovative approach based on a therapeutic vaccine. The phase 1/2 clinical trial launched in November 2021 will look at the safety and tolerability of the vaccine and the dose needed to elicit a good immune response in 24 patients, with the first results expected in 2023.
Oncode is particularly proud of this new milestone. Since its foundation in 2018, the institute has focused on funding fundamental cancer research and translating its results into practical applications for patients. Oncode offers various funding opportunities to accelerate this translation. The vaccine that will be tested is a new product. Oncode recognized the potential of the basic research finding early on and was able to utilize its TechDev fund to enable quick maturation of the technology, which was promptly followed by the CPoC grant.
Chris de Jonghe (Oncode): “It took only three years from the first publication of the research results to the start of this clinical trial. This underlines Oncode's mission to accelerate the translation of fundamental research into new treatments for patients. And of course, we hope for positive outcomes for patients with lung cancer."
Oncode Oncology Bridge Fund
Bridge fund 101: The Oncode Oncology Bridge Fund, managed by Oncode B.V., is an investment fund of €7.2M that provides pre-seed and seed capital to commercially viable enterprises originating from within the Oncode community to help translate their research ideas into market-ready investment opportunities. This can include new therapeutic interventions, diagnostic screening tools and services, biomarkers, research tools or services that will benefit either cancer patients or cancer research in general. Early-stage investments are accompanied by professional intellectual property management, follow-on financing, technology de-risking, and where possible, preliminary clinical validation. Additionally, the Oncology Bridge Fund prepares new enterprises for follow-on investments from private investors such as ‘angels’ or venture capitalists. Oncode B.V. has committed €1.1M of investment capital in 7 spin-off companies, which currently employ 17 FTEs. In addition, 8 Oncode projects (or technology opportunities) are in the ideation/validation stage prior to possibly launching as spin-off companies. In 2021, the Oncology Bridge Fund committed €600K of investment capital in 2 spin-off companies.
Checking back with Immagene: Last year, Oncode and the NKI proudly launched Oncode’s 5th spin-off; Immagene B.V. Originating from the lab of OI Prof. Daniel Peeper and Prof. Christian Blank (both NKI), the company is focused on developing next-generation precision immuno-oncology (IO) treatments. In 2021, the spin-off announced it had successfully raised seed financing to advance its next generation IO therapeutics. BOM Brabant Ventures joined as a new investor with additional support from existing investors Swanbridge Capital and Oncode Oncology Bridge Fund. The company will use the new funding to further develop its proprietary pipeline of targeted immunotherapies for cancer patients utilizing its Immunogram approach. This approach identifies limitations of state-of-the-art cancer immunotherapies, and uses guided target identification and patient stratification to enhance therapeutic outcomes.
The Immagene enterprise grew with the appointment of Jac Wijkmans, who brings extensive drug development experience, as Chief Scientific Officer. Under his leadership, multiple drug candidates have been optimized and selected for pre-clinical and clinical studies.
Dr. Maarten Ligtenberg (CEO Immagene): “I am excited that this syndicate of investors has come together to support the further development of our IO programs, and I’d like to welcome BOM Ventures as investor. I am especially pleased that industry veteran and experienced R&D executive Jac Wijkmans will be joining our team as CSO to direct our drug development endeavours.”
Mercedes Tuin (Investment Manager at BOM): “Immagene’s platform-based target selection has shown the potential to identify novel targets for which it is developing new small molecules for effective immunotherapy in cancer. This approach fits well with our focus and the strength of the local ecosystem in IO and precision medicine. We are excited to work with the team to advance their ground-breaking therapies.”
Oncode and NKI’s second spin out: Following the launch of Immagene from the NKI in 2020, Oncode and the NKI launched their second joint spin out - Oncosence - in 2021, a company building on 5 years of research from OI Rene Bernards, who focuses on understanding senescence and its role in tumour biology.
The company is based on breakthrough findings from the Bernards lab, showing that certain types of cancer can be treated with what is called ‘the one-two punch’ approach. In a 2019 Nature publication, Bernards showed that senescence can be induced by one drug, followed by a second drug to kill the senescent cancer cells. The launch of Oncosence coincided with the onboarding of a management team that will execute ideas to develop this therapeutic combination efficiently and at pace. With targets already identified and validated, and an initial investment from the Oncode Bridge Fund, the company is now gearing up to raise additional funds to develop the targets clinically.
Rene Bernards (NKI): “What makes Oncosence unique is that we are trying a completely new approach to the treatment of cancer that relates to the induction of senescence for cancer therapy. Until now this has never been done.”
Oncode’s latest spin-off: In 2021, Oncode Institute and ArgoBio teamed up with OI Madelon Maurice at UMC Utrecht to launch Laigo Bio, a new company in the emerging field of target protein degradation. Both the Oncode Bridge Fund and ArgoBio invested funds to further develop Laigo Bio’s proprietary pipeline of SureTACsR targeted immunotherapies.
Prof. Maurice had already discussed the potential of the technology with Oncode business developer Emil Pot in 2019. Quickly recognizing the potential, Oncode secured the IP using its IP-fund. Prof. Maurice subsequently applied for TechDev funding, enabling her to obtain Proof-of-Concept (PoC) for the technology platform. In the meantime, Oncode and French ‘start up studio’ ArgoBio had been discussing the potential of working more closely together to support and fund innovative early-stage projects. The SureTACsR technology of Prof. Maurice fitted perfectly with the ambitions of both the Oncode Bridge Fund and ArgoBio.
The SureTACsR technology platform is a novel membrane protein degradation approach applicable to a broad scope of disease applications. The primary focus for applications lies in oncology but the technology has the potential to be applied in parallel programmes in neuro-inflammation and neuro-degenerative diseases. In contrast to other small molecule approaches, the platform results in an efficient and sustained degradation of target receptors, potentially resulting in clinical efficacy superior to the modalities currently being employed by other emerging protein degradation technologies.
Initially driven by Madelon Maurice, who will join as Principal Investigator, Laigo Bio is gearing up for preclinical lead development in the coming months, generating proprietary biologics for a selection of targets to showcase the technology’s potential. Laigo Bio receives strong support from seasoned entrepreneurs Neill Moray Mackenzie at ArgoBio and Emil Pot at Oncode, who will prepare the company for a Series A investment round to initiate first clinical studies in 2025.
Dr. Neill Moray Mackenzie (ArgoBio): “This is exactly why we put ArgoBio together last year – to fund these early-stage opportunities. I am especially pleased that Madelon Maurice, a renowned key opinion leader in the field, is leading this novel approach to protein degradation which has great potential to open up a completely new biology in the field of cancer therapy.”
Managing the Oncode Oncology Bridge Fund: Since its inception in 2019, the Oncode Oncology Bridge Fund (OBF) has been managed by fund manager Shobhit Dhawan. Dhawan brings with him broad experience in business development and investment management. Since its launch, the fund has made investments in 7 companies, with a full pipeline of new investments expected in the coming years. While the OBF is expected to run until 2025, Dhawan and Oncode Valorization Director Chris De Jonghe are already drawing up the plans for a follow-up fund OBF-2. With Oncode’s growing ambitions and expanding pipeline of potential spin-offs, Dhawan and De Jonghe envisage that the OBF-2 fund will be larger, with contributions from Oncode’s ‘core’ public funding plus matching funds from private and/or international public partners. In 2021, the Oncode communication team sat down with Dhawan to talk about the art and challenges of linking researchers, investors, and industry to turn exciting research projects into successful companies. (You can find the full interview here).
Oncode Strategic funding support
Strategic funding support 101: Oncode’s Strategic Funding Support programme aims to help OIs navigate the funding landscape and thereby boost Oncode research funding. The programme provides tailored funding strategies for OIs and spin-off companies, offers training workshops and ‘tips & tricks’ for acquiring the most frequent types of grant, and collaborates with external parties and funding bodies on training and workshops. In previous years, Oncode business developers proactively engaged with OIs to provide funding support. In 2021, Oncode revised this strategy to create a more balanced utilization of resources, choosing to focus its attention on support through grant reviews and through the provision of (outsourced) support for strategic projects. Using this amended strategy, the programme successfully met its objectives for 2021 - adjusting resource investment to optimally utilize capacity while maintaining the quality of support. In 2021, the programme achieved a success rate of 52% (compared to 35% last year), and secured total funding of €17.4M, of which €8.6M was allocated to Oncode Institute and Investigators. Upon request, Oncode also provides support to non-Oncode researchers. A typical example is Trudy Straetemans (UMCU), for whom Oncode successfully supported an application for a KWF ‘DARE-NL infrastructure for ATMPs’ grant of €5.4M.
Other notably successful grants for which the programme provided support include:
- NWO-Vidi grants (€800K) - Hugo Snippert (UMC Utrecht) and Jarno Drost (PMC)
- NWO-Vici grant (€1.5M) – Michiel Vermeulen (Radboud University)
- ERC Starting grant (€1.5M) – Julie Nonnekens (Roland Kanaar group, Erasmus MC)
- KWF Young Investigator grant (€615K) - Florijn Dekkers (Anne Rios group, PMC)
Affordable Health Care programme
Affordable Health Care (AHC) 101: Oncode is dedicated to contributing to the affordability and sustainability of cancer healthcare solutions and aims to do so by leveraging its expertise and position in the valorization value chain to ensure affordability and sustainability obligations are included in applicable Oncode activities. Oncode therefore focuses a significant part of its strategy on this goal. Oncode’s activities in relation to AHC are accommodated in many different ways, including education and awareness, funds and programmes aimed at funding research that focuses on reducing the cost of care, health technology assessments, and socially responsible licencing policies.
In addition to its activities in this area, Oncode’s communication team also discussed the affordability of health care in general with Henk Verheul (Clinical Oncologist at Radboud UMC and Chair of the Oncode Clinical Advisory Board) and Sipko Mülder (Dutch Ministry of Health member of the management team on pharmaceutical products and medical technology). You can find the interview here.
Investing in clinical proof-of-concept to contribute to affordable health care: Oncode has set itself the objective to ensure that 20% of the clinical activities within its CPoC programme are focused either on personalized medicine (patient stratification) or drug repurposing. An analysis of Oncode’s clinical portfolio in 2021 showed that over 58% of clinical projects contribute to AHC. More specifically, 47% of CPoC projects investigate patient stratification and 29% drug repurposing. Below are two examples of how Oncode’s CPoC programme is contributing to AHC.
BASALT study (JP. Medema, Amsterdam UMC): In partnership with ZonMw, Oncode has invested in 3 CPoC projects dedicated to AHC (pre)clinical research with a total budget of €~1.5M. One of these studies, titled ‘Blood-borne assessments of stromal activation to guide therapy in esophageal adenocarcinoma (BASALT)’ and awarded funding of €594K over three years, started in 2021. The study was initiated by OI Jan Paul Medema (Amsterdam UMC) in collaboration with clinician Hanneke van Laarhoven (Amsterdam UMC) and aims to study the safety and efficacy of a new combination therapy and validate a biomarker for esophageal adenocarcinoma - a type of cancer with poor prognosis (median survival just over 3.5 years). A positive outcome from this study will provide a new treatment regimen and a much-needed stratification tool that have the potential to improve the outcome of currently available therapies.
HDAC inhibitor Vorinostat in resistant BRAF V600 mutated advanced melanoma (Rene Bernards, NKI): Patients with advanced BRAF V600 mutated (BRAFm) melanoma develop resistance to BRAF inhibitors (BRAFi) and/or MEK inhibitors (MEKi) 6 to 14 months after beginning treatment. This is often associated with secondary mutations in the MAPK pathway (for example, NRAS/KRAS), leading to reactivation of the pathway. Preclinical studies in cell lines and mice have shown that treatment of BRAFi-resistant BRAFm melanoma with Vorinostat leads to selective cell death of BRAF inhibitor resistant cells only, and to a remarkable reduction of tumour volume. Bernards, together with clinician Sophie Wilgenhof (NKI-AVL), has worked on this clinical Proof-of-Concept trial in patients with advanced BRAF V600 mutated melanoma who developed resistance to BRAF inhibitors and/or MEK inhibitors. For this patient group no rational treatment is currently available. Within the study, which included 18 patients, ctDNA was used as a biomarker to detect emerging clones resistant to BRAF inhibitors so that patients could be switched to a short-term purging treatment with Vorinostat before BRAF-MEK inhibition was reintroduced. This short-term treatment with Vorinostat has led to promising results. If this new therapy proves to be potentially useful, the study will be completed using external funding. A follow-up phase 2 clinical study is expected, with the aim of providing clear improvements to the current standard of care. Oncode supported this project by analyzing its potential cost-effectiveness in an early-stage Health Technology Assessment (HTA). This HTA suggested that the addition of Vorinostat may be a cost-effective intervention, via a shorter treatment cycle. Further research will focus on the clinical effectiveness of Vorinostat in combination with BRAF/MEK inhibition, the feasibility to detect resistance in an early phase, and survival and quality of life compared to the current standard of care.
Providing the tools and expertise to enable drug repurposing research: Drug repurposing is an effective approach to rapidly identify novel indications for known drugs and compounds. To support researchers in bringing novel therapeutic applications to patients at affordable cost, Oncode has acquired a next-generation Drug Repurposing Library containing ~6,000 candidate drugs in various stages of clinical development (abandoned, off-patent, launched, etc.). To enable all Oncode researchers to access the library, Oncode has set up the Drug Repurposing programme. This programme funds drug repurposing compound screens and provides the technical infrastructure and expertise required to perform the screens. In addition, copies of the library are provided to both Oncode and non-Oncode researchers who have the means and expertise to perform the screens themselves. The programme was initiated in late 2019, and since then a total of 14 screening programmes from OIs have been approved, of which 6 were undertaken in 2021. Two centres within Leiden UMC and NKI have unique drug screening expertise and are able to provide researchers with tailored guidance and support as well as access to a multitude of different assays. Read about the experiences of OI Roland Kanaar with the NKI’s centre of expertise here. The library has also been provided to 3 non-Oncode research projects, one of which was aimed at finding therapeutic solutions to COVID-19. Below are two success stories of the Oncode Drug Repurposing programme:
Repurposed drugs enter the fight against breast cancer: Estrogen receptor (ER) is considered the main driver in ~70% of all breast cancer cases, and multiple therapeutic options have been developed to block ER action. Although considered a success, a substantial proportion of these patients will relapse after treatment, often resulting in metastatic disease that cannot be cured. Importantly, in ~80% of all metastatic endocrine-resistant cases, ER continues to be expressed and is still considered the driver. OI Wilbert Zwart (NKI) used Oncode’s drug repurposing library to identify vulnerabilities in endocrine-resistant breast cancer cells, potentially revealing new therapeutic options for these patients. Using a carefully set up screening assay, the entire drug reproposing library was tested, resulting in a broad set of compounds with potential tumour cell proliferation inhibiting properties. In a secondary, more focused screen, these compounds were validated, revealing a large subset of compounds that proved to be effective in endocrine-resistant breast cancer cell lines. Closer investigation of the top hits revealed that several of these compounds belonged to a class of drugs known to have an effect on one particular pathway.
Importantly, several of the drugs of interest are already clinically applied in the treatment of other cancers. While it remains untested whether these compounds would be clinically effective in endocrine-resistant breast cancers, the current clinical application of these drugs clearly has the potential to accelerate the route towards clinical trials of the study findings. Zwart is now validating the drugs in cell cultures derived from metastatic breast cancer patients, as well as in patient-derived xenograft mouse models. In parallel, these results have been discussed with the NKI Clinical Trials Unit, who are now designing a clinical trial to confirm the findings in a clinical setting as soon as pre-clinical validations have been successfully completed.
Ruud Delwel’s quest to combat AML: The research group of Ruud Delwel (Erasmus MC) is mainly focused on molecular defects driving the development of acute myeloid leukemia (AML). AML is a rare but highly fatal form of leukemia that mostly affects elderly people.
“When you look at AML cells under a microscope, they all look alike. But patients with AML can respond very differently to treatment: There are individuals that respond well to treatment. There’s a group that doesn’t respond to the treatment at all. Unfortunately, the biggest group of patients respond well to treatment at first, but the cancer comes back after a few years and the outlook for those patients is then very poor”, explains Delwel.
At the biological and molecular level, AML is not one disease. Different subtypes with distinct abnormalities can be distinguished based on different genetic defects. For many years, Delwel’s group focused on one of the most aggressive forms of AML – one that is driven by overexpression of the EVI1 oncogene. To combat this aggressive form of AML, the Delwel group developed screening assays to identify drugs that can interfere with oncogene overexpression. This is where the Oncode Drug Repurposing programme came into play. Delwel’s group was granted a drug repurposing screen, which was performed in 2021 with the help of the Oncode centre of expertise at NKI.
Following an initial drug screen with the library, 100 compounds were selected for a secondary dose response series. Based on the data from these screens several compounds were selected that had an effect on EVI1.
“We will now focus our efforts on understanding the mechanisms behind the action of these compounds. We are very excited to have found several molecules that have an effect on a previously undruggable oncogene, something that may hold great promise for the future treatment of this subgroup of AML patients. Moreover, if one of the compounds proves to be clinically relevant in the future, impact can be made relatively quickly and cost effectively since many of the compounds in the library have been either approved or are in late-stage clinical development for other indications,” says Delwel.
Socially Responsible Licensing of Oncode innovations: Oncode contributed to setting up the Socially Responsible Licensing (SRL) policies and toolkit of the Netherlands Federation of University Medical Centres (NFU) and was one of the first to endorse them. The Socially Responsible Licensing (SRL) guidelines and toolkit offer Dutch knowledge institutions a common basis for discussions with other parties about the future use of their patented knowledge. Along with the usual agreements about rights and obligations, the SRL pays explicit attention to societal objectives, such as the effective availability of products and services.
Since 2019, Oncode has explicitly incorporated SRL principles in its license agreements and has negotiated adherence to the guidelines for agreements in which they are applicable. The table below shows the number of licenses Oncode has brokered during its years of operations, and the number of times the SRL guidelines were fully applicable and subsequently incorporated. It is of note that SRL guidelines are only fully applicable to those agreements relating to therapies or diagnostics (not all guidelines are applicable/relevant to agreements dealing with research or software tools). In 2021, the Dutch Ministry of Health requested an assessment of Oncode’s SRL performance and Drug repurposing activities from Oncode’s IRC. The assessment was completed in February 2022, with the IRC rating Oncode’s performance as ‘Good’ to ‘Very Good’. The IRC noted that: “although the implementation of SRL language in licenses is at an early stage, Oncode helps to set the agenda on making price an important parameter in the development of therapeutics”.
Health Technology Assessments: Oncode aims to address the cost effectiveness of drugs at a very early stage in their development. To achieve this, the Oncode TechDev fund has supported early Health Technology Assessments (HTAs) for certain projects. HTAs measure the added value of a new treatment compared to the existing standard of care. It evaluates whether a new drug works better, equally well, or worse than existing alternatives, based on its therapeutic effect, potential side effects, influence on quality of life, and means of administration. In addition, it also assesses the cost implication of a new treatment for the patient and its impact on the healthcare system. HTAs are typically used by health authorities and policy makers as an evidence-based auxiliary method to make reimbursement decisions about new treatments and is therefore usually only implemented by drug developers in the late stages of development. Oncode, in collaboration with Thinc at UMCU, is pioneering the use of HTA analyses at a very early stage of drug development in order to determine a drug’s cost-sensitivity throughout the entire drug development cycle and guide/adjust development routes accordingly. Oncode financed 5 HTA analyses up to the end of 2021, the outcomes of which have helped guide Oncode’s decision process for future project development/investments.