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Just nu utvärderar Scandion Oncology sin ledande kandidat SCO-101 i två kliniska studier, en med läkemedelsresistent metastaserande kolorektalcancer och en där kandidaten används som första linjens behandling i patienter med icke-operabel bukspottkörtelcancer. Förra veckan presenterade bolaget även en poster vid San Antonio Breast Cancer Symposium, som är den största årliga bröstcancerkonferensen. Postern beskriver SCO-101s förmåga att göra antiöstrogenresistenta bröstcancerceller mottagliga för behandling igen. BioStock kontaktade Scandion Oncologys CMO Peter Michael Vestlev och CTO Jan Stenvang för att få veta mer om arbetet med detta och dess potentiella konsekvenser.

Bröstcancer är den vanligaste cancerformen hos kvinnor med fler än 560 000 nya rapporterade fall i Europa varje år. Dessutom kommer 15–20 procent av bröstcancerpatienterna att få metastaser i andra organ. Kvinnor som lider av metastaserad bröstcancer behandlas ofta med en typ av läkemedel som kallas antiöstrogener och som normalt blockerar de skadliga växtstimulerande effekterna som östrogen har på bröstcancerceller. Dessvärre kommer dock nästan alla dessa patienter vid någon tidpunkt att bli resistenta mot behandlingen.

Scandion Oncology presenterade på viktig bröstcancerkonferens

Det danska bioteknikbolaget Scandion Oncology utvecklar läkemedel som riktar sig mot molekylära resistensmekanismer i cancer. Bolagets ledande läkemedelskandidat SCO-101 vänder resistens mot vanligen använda kemoterapeutiska läkemedel. Just nu utvärderas SCO-101 i en klinisk fas II-studie med patienter som lider av läkemedelsresistant metastaserad kolorektalcancer samt i en fas Ib-studie i kombination med första linjens behandling med kemoterapi i patienter med metastaserad bukspottkörtelcancer.

Medan fas II-studien pågår utforskar bolaget även SCO-101s potential inom andra cancerindikationer, inklusive bröstcancer, efter att prekliniska data har visat att SCO-101 kan vända antiöstrogenresistens. Förra veckan deltog bolaget virtuellt i San Antonio Breast Cancer Symposium (SABCS), en internationell konferens med fokus på bröstcancerforskning som pågick mellan 8–11 december. Den 9 december presenterade Scandion Oncology sina senaste prekliniska data som visar SCO-101s förmåga att göra antiöstrogenresistenta bröstcancerceller mottagliga för behandling.

»Worldwide, breast cancer is the most common malignancy among women. Of the patients who are treated for breast cancer approximately 20 – 40 per cent will develop advanced breast cancer and of these patients nearly all will succumb to the disease. […] Our vision is that by introducing SCO-101 as an add-on to endocrine treatment of breast cancer patients, we can improve the effect of antioestrogens and thus give breast cancer patients hope of a long-lasting effect of treatment« — Peter Michael Vestlev, CMO Scandion Oncology

Arbetar mot målet att nå klinisk validering

Scandion Onocologys data är tillräckligt lovande för att motivera bolaget till att genomföra en utvärdering av SCO-101 med antiöstrogenresistens i klinisk miljö. I somras fick Scandion Oncologys idé för det kliniska projektet ytterligare dragkraft när bolaget tillsammans med samarbetspartnerna 2cureX och Erasmus University Medical Center, fick ett Eurostars-bidrag på 800 000 EUR för att sätta igång projektet.

Idén är att forskarna vid Erasmus Medical Center i Rotterdam ska genomföra sofistikerade molekylära analyser för att klarlägga de molekylära mekanismer som ligger bakom hur SCO-101 motverkar antiöstrogenresistens. 2cureX att använda bidraget för att identifiera de patienter som har den högst sannolikheten för att få klinisk nytta av SCO-101 med hjälp av 2cureX funktionella precisionsmedicinstest IndiTreat. Det här arbetet skulle kunna leda till en klinisk fas Ib studie i vilken kvinnor med metastaserande bröstcancer exponeras för ökande doser av SCO-101 tillsammans med standarddosen antiöstrogener.

CMO och CTO kommenterar projektets betydelse

För att få veta mer om SCO-101s potential att motverka anitöstrogenresistens kontaktade BioStock Scandion Oncologys CMO Peter Michael Vestlev samt CTO Jan Stenvang.

Peter Michael Vestlev, from a medical perspective, why is breast cancer so difficult to treat and why is SCO-101 a strong candidate for relieving some of the burden on breast cancer patients?

– The biggest challenge in the treatment of breast cancer is the development of resistance to the treatments that we can currently offer. Worldwide, breast cancer is the most common malignancy among women. Of the patients who are treated for breast cancer approximately 20 – 40 per cent will develop advanced breast cancer and of these patients nearly all will succumb to the disease.

– Patients with oestrogen receptor-positive disease are primarily treated with antioestrogens, of which there are three classes in common use: aromatase inhibitors, tamoxifen (an oestrogen receptor inhibitor) and Fulvestrant (an oestrogen receptor inhibitor and degrader). The treatment may be combined with a CDK 4/6 inhibitor.

Peter Michael Vestlev, CMO Scandion Oncology

– A few patients have a life-long good response with this treatment, however, for the majority of patients, the breast cancer develops resistance to such treatment. It is still not known exactly how breast cancer cells can develop endocrine treatment resistance, and presently there are no approved treatments that directly interfere with this type of resistance. However, when breast cancer cells have developed resistance to endocrine treatment, there is only chemotherapy left as an option, an option that is more toxic and to which the breast cancer will eventually also become resistant.

– It is therefore of extreme importance that we develop new treatment methods that can be used to extend the duration of time the endocrine treatment is effective in the patient. If we can prolong the duration of antioestrogen efficacy, we may be able to turn breast cancer into a disease that the women can live with, but not die from. SCO-101 may be such a drug since we know from our preclinical data that SCO-101 can block endocrine resistance in breast cancer and thus make the breast cancer cells sensitive to antioestrogens again. Our vision is that by introducing SCO-101 as an add-on to endocrine treatment of breast cancer patients, we can improve the effect of antioestrogens and thus give breast cancer patients hope of a long-lasting effect of treatment.

Jan Stenvang, does the mechanism of action of SCO-101 in metastatic breast cancer differ at all compared to metastatic colorectal cancer?

– In colorectal cancer, we have identified molecular targets that are involved in the SCO-101 reversal of resistance to some of the types of chemotherapy applied to treat colorectal cancer patients. However, the antioestrogens applied to treat breast cancer patients work by very different molecular mechanisms, and the underlying reasons for resistance to antioestrogens appear to be different from the chemotherapy applied in colorectal cancer. In the ongoing Eurostars project, Erasmus University Medical Centre will conduct detailed molecular analyses aiming to identify the essential players in SCO-101 mediated re-sensitisation to antioestrogens.

Jan Stenvang, CTO Scandion Oncology

With colorectal cancer, Scandion Oncology has identified potential biomarkers for predicting which patients would best benefit from SCO-101. Could these biomarkers work in breast cancer patients?

– It is obvious that we will also analyse if any of these biomarkers could be of predictive value in breast cancer. As mentioned, we aim to identify molecules that are crucial for the ability of SCO-101 to re-sensitize breast cancer cells to antioestrogens. The molecules we identify are all very strong candidates for predictive biomarker and will be investigated further in biomarkers assays both using archived breast cancer material and biopsies from patients entering the planned clinical breast cancer studies.

When do you expect to begin clinical evaluation of SCO-101 in breast cancer patients?

– As we have communicated in our recent Prospectus, we will explore the possibility to conduct a phase Ib (dose range finding) clinical trial. In this trial metastatic breast cancer patients would continue their antioestrogen treatment but now in combination with increasing doses of SCO-101. When the maximal tolerable dose of SCO-101, given together with antioestrogens, has been defined, Scandion Oncology intends to initiate a randomized study in this patient population. considering the huge medical need, the large preclinical and clinical knowledge we have internally in antioestrogen resistant breast cancer and our excellent external collaborators, we look very much forward to the continued development in this project.

Could you give a quick overview of the data that was presented at the SABCS conference?

– What we demonstrated in the Poster at SABCS was preclinical proof-of-concept data showing that SCO-101 in combination with antioestrogens re-sensitised antioestrogen resistant breast cancer cells. This was true for different models of antioestrogen resistant breast cancer model systems, and for both of the two clinically applied antioestrogens; Fulvestrant and Tamoxifen.

Finally, how far down the road can you expect to get with the project with the funds from the EuroStars grant?

– With the Eurostars funding we can conduct detailed and sophisticated analyses to reveal the mechanism of action for SCO-101 in antioestrogen resistance and to identify potential biomarkers. Furthermore, 2cureX is a partner in the Eurostars project, and they will conduct studies of human breast cancer biopsies to identify responders and non-responders to the combination of SCO-101 and antioestrogens. So, we will aim for both a classical biomarker approach and a functional predictive assay to eventually optimize the selection of breast cancer patients that are most likely to respond.

– Moreover, the Eurostars funding will also support us when we conduct the clinical dose range finding phase 1b study to investigate the safety and optimal dose of SCO-101.

– Finally, we have very recently obtained an Intention to Grant notice for our EP patent application on SCO-101 and antioestrogens (divisional) EP application no. 19205104.3. The notice of the Intention to Grant means that the European Patent Office (EPO) intends to approve the patent application, but that a number of administrative steps remain before a final decision to grant is issued.

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