4873 English

Resistens mot antiöstrogenläkemedel är ett stort problem i behandlingen av bröstcancer. I ett försök att lösa detta har Scandion Oncology, vars läkemedelskandidat SCO-101 har potential att motverka sådan resistens, gått samman med 2cureX, ett bioteknikbolag med expertis inom funktionell precisionsmedicin vars IndiTreat-test kan hjälpa till att stratifiera patienter baserat på SCO-101-känslighet i en planerad klinisk prövning. De två danska bolagen har fått ett Eurostars-bidrag på 800 000 euro, delat med Erasmus University Medical Center, för att genomföra ytterligare prekliniska studier samt planera och genomföra den kliniska prövningen.

Bröstcancer är den vanligaste typen av cancer hos kvinnor med mer än 560 000 nya fall i Europa varje år. Cirka 15–20 procent av patienterna med bröstcancer kommer att uppleva metastaserande sjukdomar, och grundpelaren i dagens medicinska behandling är endokrin behandling, alltså hormonbehandling.

Målet med endokrin behandling är att blockera könshormoner, i detta fall östrogen, från att stimulera tillväxten och spridningen av cancerceller. Tyvärr kommer nästan alla bröstcancerpatienter med metastaser att någon gång att bli resistenta mot sådan behandling.

SCO-101 skulle kunna motverka antiöstrogen resistens

När det gäller kampen mot cancerläkemedelsresistens engagerar sig danska Scandion Oncology i arbetet för att hitta innovativa lösningar. Bolaget driver flera projekt med syfte att utveckla läkemedel som kan övervinna resistens mot kemoterapi och huvudkandidaten SCO-101 har nått klinisk fas II inom metastaserande kolorektal cancer.

SCO-101 är dock inte specifik för en viss typ av cancer utan kandidaten har levererat lovande prekliniska data inom flera cancerindikationer, inklusive pankreascancer och bröstcancer där SCO-101 kunde häva s.k. förvärvad resistens mot kemoterapi eller antiöstrogener.

För att lära sig mer om dess verkningsmekanism har Scandion Oncology ingått ett samarbete med Erasmus University Medical Center i Rotterdam, Nederländerna, vars team kommer att analysera exakt hur SCO-101 blockerar antiöstrogenresistensen hos bröstcancerceller.

IndiTreat stratifierar patienter för kliniska prövningar

För att vidare utforska de potentiella fördelarna med SCO-101 vid bröstcancer har Scandion Oncology inlett ett samarbete med ett annat innovativt danskt bioteknikbolag som fokuserar på onkologi – 2cureX.

2cureX är en pionjär inom området funktionell precisionsmedicin (FPM) tack vare sitt IndiTreat-test ett kliniskt test som kan förutsäga vilken behandling som bäst matchar varje enskild cancerpatient. Dessutom kan IndiTreat även användas för att identifiera vilka patienter som är resistenta mot specifika cancerläkemedel. I samarbetet med Scandion Oncology ska IndiTreat användas för att avgöra vilka patienter som är resistenta mot antiöstrogenbehandling och som därmed skulle kunna dra nytta av behandling med SCO-101 i kombination med antiöstrogener.

2cureX har validerat IndiTreat i patienter med kolorektalcancer, och efter ett intensivt Early Access Program är planen att lansera IndiTreat fullt ut på den europeiska marknaden under andra halvåret 2020. Även om 2cureX huvudfokus hittills har varit kolorektalcancer så förväntas IndiTreat fungera även inom andra cancerindikationer, inklusive bröstcancer, där det kliniska behovet knappast kan underskattas.

Detta gör IndiTreat till en lämplig precisionsmedicinskt komplement i den planerade kliniska prövningen med SCO-101 inom antiöstrogenresistent bröstcancer. Tack vare FPM-tekniken kan patienter stratifieras baserat på SCO-101-känslighet under den planerade studien, vilket begränsar antalet patienter som behöver inkluderas. I allmänna termer innebär en sådan stratifieringsmöjlighet att nya läkemedel snabbare kommer till patienter, samtidigt som kostnaderna sänks – en win-win-win-win för patienterna, klinikerna som utför studien, bolagen som utvecklar behandlingarna och samhället som helhet.

Projekt erhåller Eurostars bidrag

De två bolagens projekt har tilldragit sig uppmärksamhet från Eurostars, ett program som drivs gemensamt av EUREKA och Europeiska kommissionen med syfte att stödja innovativa internationella projekt som leds av FoU-drivna små och medelstora bolag. Scandion Oncology och 2cureX, tillsammans med Erasmus University Medical Center, har nu tilldelats ett bidrag från programmet om 800 000 euro för att finansiera projektet – ett tecken på att internationella finansiärer ser det som ett innovativt projekt med intressant potential.

BioStock har varit i kontakt med både Nils Brünner, Scandion Oncologys vd och Ole Thastrup, 2cureX vd för att få veta mer om projektet och samarbetet.

»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, vd för 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?

Nils Brünner, vd Scandion Oncology

– 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, vd för 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.

Ole Thastrup, vd 2cureX

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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