Antioestrogen drug resistance is a major obstacle in the treatment of breast cancer. Scandion Oncology’s drug candidate SCO-101 has the potential to counteract such resistance, and the challenge has brought the biotech company together with the Functional Precision Medicine expert 2cureX, whose IndiTreat test may help stratify patients based on SCO-101 sensitivity in a planned clinical trial. The two Danish biotechs have received a Eurostars grant of 800,000 EUR, shared with Erasmus University Medical Centre to perform additional preclinical studies and to set up and run the trial.
Breast cancer is the most common type of cancer in women with more than 560,000 new cases in Europe each year. About 15-20 per cent of breast cancer patients will experience metastatic disease, and the mainstay in medical treatment is endocrine therapy.
The goal of endocrine therapy is to block sex hormones, in this case oestrogen, from stimulating the growth and spread of cancer cells. Unfortunately, almost all metastatic breast cancer patients will, at some point, become resistant to such treatment.
SCO-101 may counter antioestrogen resistance
When it comes to cancer drug resistance, Danish Scandion Oncology are committed to finding innovative solutions. The biotech company has several ongoing projects with the aim of developing drugs that can overcome resistance to chemotherapy, and its top candidate SCO-101 has reached phase II clinical trials in metastatic colorectal cancer.
However, SCO-101 is not specific to one type of cancer, and, in fact, the candidate has delivered promising preclinical data in other cancer indications, including, pancreatic cancer and breast cancer, where SCO-101 has been shown to reverse acquired resistance to chemotherapy or antioestrogens.
To learn more about the mode of action in question, Scandion Oncology has entered a collaboration with Erasmus University Medical Center in Rotterdam, the Netherlands, whose team will be dedicated to analyse exactly how SCO-101 blocks the antioestrogen resistance of breast cancer cells.
IndiTreat will stratify patients for clinical trials
However, to pursue the potential benefits of SCO-101 in breast cancer even further, Scandion Oncology has partnered with another innovative Danish biotech focused on oncology – 2cureX.
2cureX are known as pioneers in the field of Functional Precision Medicine (FPM) thanks to their clinical test, IndiTreat – a tool able to predict which treatment best matches each individual cancer patient. Not only that, but IndiTreat could potentially help identify which patients are resistant to specific cancer drugs, and, for this particular collaboration, which patients are resistant to antioestrogen therapy and could benefit from receiving SCO-101 treatment in combination with antioestrogens.
2cureX have been validating IndiTreat in colorectal cancer patients, and, after an intense Early Access Program, IndiTreat is expected to fully launch on the European market during the second half of this year. While colorectal cancer has been 2cureX’s main focus, IndiTreat is expected to perform as intended within other cancer indications as well, including breast cancer, where the clinical need is difficult to understate.
This makes IndiTreat a suitable precision medicine companion for the planned clinical trial with SCO-101. Thanks to the FPM technology, patients can be stratified based on SCO-101 sensitivity during the planned clinical trial, thus limiting the number of patients needed to be enrolled in the trial. In general terms, this implies bringing new drugs to patients faster, all while lowering the costs – a win-win-win for patients, clinicians running the trials, the companies running the show and society as a whole.
Project receives Eurostars grant
The idea of the project has caught the eye of Eurostars, a joint programme between EUREKA and the European Commission aimed at supporting international innovative projects led by R&D-performing SMEs. Scandion Oncology and 2cureX, along with Erasmus University Medical Center, recently received a grant from the programme of 800,000 EUR to fund this project – a sign that this project is viewed from international funders as highly innovative and with exciting potential.
BioStock was able to get in touch with both Nils Brünner, Scandion Oncology’s CEO, and Ole Thastrup, 2cureX’s CEO, to learn more about the project and collaboration.
»Knowing the mode of action of SCO-101 in restoring antioestrogen sensitivity in breast cancer is key to the development of molecular predictive biomarkers. For example, if we show that SCO-101 reverses antioestrogen resistance by blocking molecule XX, we will develop new test systems to secure that patients being offered SCO-101 treatment are those where molecule xx is present in the cancer cells. This approach is called Personalized Medicine« — Nils Brünner, CEO of Scandion Oncology.
Nils Brünner, you must be excited about this project and collaboration. Could you give us more background about the project and tell us more about how it all started?
– As a young oncologist, I spent a long time in the breast cancer section and here I learned about drug resistance, whether it was resistance against chemotherapy or antioestrogens. I got the opportunity to move to USA, where I performed research on antioestrogen resistance at the National Cancer Institute. Being back to Denmark I continued my clinical work, but now in a shared position with both patient treatment and cancer research. We were granted a Danish National Science Foundation grant within cancer drug resistance, and during this period we identified SCO-101 as a potential drug to revert chemotherapy or antioestrogen resistance. Now at Scandion Oncology it was natural also to continue the antioestrogen work.
– During the last 30 years, I have been actively involved in the European Organization for Research and Treatment of Cancer and during these years I have had a scientific collaboration with the Rotterdam Group. They are experts in molecular studies of breast cancer, so it was natural to invite them into this Eurostars application.
– When I worked as Professor at University of Copenhagen, Ole Thastrup, CEO and founder of 2cureX was my Institute leader. We had many very exciting and fruitful discussions on cancer research and especially on prediction of treatment response in cancer. With Scandion oncology’s drug development program, it was obvious to invite 2cureX into the Eurostars application.
So far, Scandion Oncology has mainly focused on colorectal cancer. What influenced your decision to move into breast cancer, and why is this an important step for Scandion Oncology?
– At Scandion Oncology we develop so-called add-on drugs, meaning drugs to be given together with other therapies. We focus on anti-cancer drugs in general, and not on a specific cancer form. In the case of antioestrogens, the cancer type is breast cancer, where antioestrogens are a major component of the routine treatment. Antioestrogens belong to the family of endocrine treatment of cancer. Another family member is anti-androgens, which are drugs that block the cancer-stimulating properties of the male sex hormone testosterone. Antiandrogens are frequently being used to treat prostate cancer, but even here, the major problem is the almost inevitable development of drug resistance.
What will be the first step in this project, and when can we expect this to happen?
– In such a collaborative project, it is very important that all partners are aligned with the individual tasks. So, the first task is to hold a collaboration meeting where the practical details are discussed. However, we have already transferred the first breast cancer cell lines to Rotterdam to provide them with this tool for their coming investigations. In regards to 2cureX, we have also provided breast cancer cell lines to them for 3D growth in the IndiTreat assay.
– Scandion Oncology has, in addition, contacted relevant Danish oncologists to discuss the planned clinical phase Ib study where breast cancer patients with metastatic and antioestrogen-resistant cancer disease will receive increasing doses of SCO-101 in combination with antioestrogens. The primary aim will be safety and to define the concentration of SCO-101 to be given together with standard dose antioestrogen in the subsequent phase II study. In this phase II study, efficacy will be the primary end-point. My plan is that the application to the Danish medicines Agency will be ready in the early fall this year, with trial start during Q4/2020-Q1/2021.
How will understanding SCO-101’s mode of action benefit the clinical trial and further projects with this candidate, if any?
– Knowing the mode of action of SCO-101 in restoring antioestrogen sensitivity in breast cancer is key to the development of molecular predictive biomarkers. For example, if we show that SCO-101 reverses antioestrogen resistance by blocking molecule XX, we will develop new test systems to secure that patients being offered SCO-101 treatment are those where molecule xx is present in the cancer cells. This approach is called Personalized Medicine.
Will Erasmus University Medical Center contribute to the project in any other way?
– It would be great if we could have the clinical department at Erasmus Medical Center to participate in the clinical study. We have initiated contact with this department already.
Could you give us your thoughts on what it means for Scandion Oncology to work with an innovative company like 2cureX?
– 2cureX is providing a very important contribution to the Eurostars project. By using the IndiTreat assay, we expect 2cureX to be able to identify those patients with the highest likelihood of obtaining benefit from SCO-101 treatment. Such an opportunity will not only spare a number of patients from continued ineffective treatment, but also be of value for the health economics.
Overall, what does this project mean for Scandion Oncology’s long-term development?
– As mentioned above, Scandion Oncology is not focusing on a particular cancer disase but instead on different anti-cancer drugs to which cancer patients frequently develop resistance. For example, if we can prove in the upcoming pancreatic cancer study that SCO-101 can revert taxane resistance, we can immediately move this information to the at least 9 other cancer forms being treated with taxanes. Scandion oncology now has the possibility due to the Eurostars grant to obtain clinical proof of concept for an additional cancer treatment being antioestrogens. If successful it will be natural to start looking at antiandrogen resistance in prostate cancer.
Finally, what is your reaction to receiving the Eurostars grant?
– I am extremely pleased. It gives us an additional opportunity to prove the value of SCO-101 in the treatment of drug resistant cancer. It is also an important independent validation of the preclinical and clinical research performed by Scandion Oncology.
»IndiTreat identifies both the treatments that are effective in the individual patient as well as the treatments to which the patient is resistant. For this project in particular, we will utilize both aspects of IndiTreat. We want to select the patients that have become resistant to endocrine therapy (antioestrogen) and subsequently see which of these where SCO-101 can alleviate the resistance« — Ole Thastrup, CEO of 2cureX.
Ole Thastrup, did Nils Brünner reach out to you for this collaboration and what was your reaction?
– Yes, Nils Brünner asked whether I felt that 2cureX could run the IndiTreat test in breast cancer – I said yes, as preliminary experiments conducted in our subsidiary in Hamburg clearly show that IndiTreat can be applied to breast cancer. Further, the project fits nicely into our strategic area of using IndiTreat in stratification of patients in clinical trials. It was therefore not difficult for me to say yes to participate in this collaboration.
2cureX has a big role to play in this project bringing your Functional Precision Medicine tool IndiTreat. Could you go into more detail about 2cureX’s, or, more specifically, IndiTreat’s role in this project?
– IndiTreat identifies both the treatments that are effective in the individual patient as well as the treatments to which the patient is resistant. For this project in particular, we will utilize both aspects of IndiTreat. We want to select the patients that have become resistant to endocrine therapy (antioestrogen) and subsequently see which of these where SCO-101 can alleviate the resistance.
– SCO-101 will in itself not kill the tumour, it will have to be given in combination with the drug to which the patient is resistant – in this case antioestrogens. 2cureX will in this project evaluate different combinations of SCO-101 and endocrine therapy. The IndiTreat test is in this way finding the combination that fits the individual patient.
How does this project fit into your overall product development?
– As stated above the present collaboration feeds into both our strategic areas: a) Patient stratification in clinical drug trials and b) Individualization of cancer treatment. We see the Functional Precision Medicine test IndiTreat as becoming an important tool during clinical trials in selecting patients being sensitive to the tested treatment – in this case SCO-101-based treatment. A long-term opportunity would be that IndiTreat will become a companion diagnostic tool that will need to run for the treatment to be approved. In order for this to materialize it is important that the IndiTreat test can be decentralized. This is where 2cureX’s newly-described automation project fits in.
With regard to the other strategic area of providing a defined treatment to the individual patient, we are currently conducting clinical validation of IndiTreat in three major cancers, including ovarian cancer. The extension of our product pipeline with breast cancer will allow us to cover the two largest cancers in women. The two cancers show a very different development, but share a clear medical need to improve treatment outcomes for patients with late stage disease.
Could you, too, share give us your thoughts on what it means for 2cureX to work with an innovative company like Scandion Oncology?
– Scandion and 2cureX share the same view that resistance in late stage cancers is a devastating problem that need to be handled in order to improve patient outcome. I have great respect for the Scandion Team headed by Nils Brünner, and their drug candidate SCO-101 could be a game-changing contribution to the treatment of cancers progressing on standard drug treatments.
– The two companies synergize with regard to technologies and have a unique opportunity to develop a complete treatment offering.
As with Scandion Oncology so far, 2cureX has mainly focused on colorectal cancer. What influenced your decision to move into breast cancer, and why is this an important step for 2cureX?
– 2cureX has received several requests for moving into other cancers. In order for us to say yes, there are two important criteria that need to be fulfilled: a clear medical need and strong clinical partners with a considerable flow of patients. An important aspect of the IndiTreat test is that the oncologists will not only receive data on their own patient, they will also have their specific patient compared to a panel of reference patients. Our collaborating oncologists see this comparative analysis to be very important for their decision process. Going into new cancer entities therefore requires dedication from both the clinical partner(s) and from 2cureX.
How will the collaboration with Erasmus University Medical Center impact 2cureX, if at all?
– Yes, Erasmus Medical Centre (Erasmus MC) is an internationally-recognized, major clinical centre that 2cureX is proud to work with. Erasmus MC is the first clinical centre in the Netherlands that 2cureX has begun a collaboration with. We look forward to support the present project and to expand collaborative activities in breast cancer.
Overall, what does this project mean for 2cureX’s long-term development goals?
– The present project fits perfect into our strategic area of using IndiTreat in patient stratification during clinical trials. We further see the development of an IndiTreat Breast Cancer Test as an important expansion of our line of IndiTreat products.
– This project’s focus on resistance feeds into a major medical problem in most cancers. 2cureX is already involved in clinical studies where patients have become resistant to standard treatments. Today we see that patients received several lines of different treatments as they become resistant to the provided treatment after some time. We would like to see IndiTreat used every time such resistance occurs. With the hope that even if these resistant patients cannot be cured, we may convert their cancer into a chronic disease.
Finally, what is your reaction to receiving the Eurostars grant?
– “Fantastic!” – the project holds some important opportunities for 2cureX in being involved in developing a new treatment that has “game-changing” potential and open for expanding IndiTreat into breast cancer. The project team established has the expertise and dedication to make this project a success.
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