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Scandion Oncology is currently evaluating its lead candidate SCO-101 in two clinical trials, one with drug resistant metastatic colorectal cancer and one as first line treatment in patients with inoperable pancreatic cancer. However, last week, the company presented a poster at the San Antonio Breast Cancer Symposium, which is the largest yearly breast cancer meeting. The poster describes the ability of SCO-101 to re-sensitise antioestrogen resistant breast cancer cells. BioStock reached out to Scandion Oncology CMO Peter Michael Vestlev and CTO Jan Stenvang to learn more about this work and its potential implications.

Breast cancer is the most common cancer in women with more than 560,000 new cases reported in Europe every year. Furthermore, 15 – 20 per cent of breast cancer patients will experience metastases to other organs. Women suffering from metastatic breast cancer are often treated with a class of drugs called antioestrogens that would normally block the harmful growth stimulating effects of oestrogen on the breast cancer cells. Unfortunately, almost all these patients will, at some point, become resistant to the treatment.

Scandion Oncology presents at major breast cancer conference

Danish biotech Scandion Oncology develops drugs that target molecular resistance mechanisms in cancer. The company’s lead drug candidate SCO-101 reverses resistance to commonly used chemotherapeutic drugs. Currently, SCO-101 is evaluated in a phase II clinical trial with patients suffering from drug resistant metastatic colorectal cancer and in a phase Ib study in combination with first-line chemotherapy in metastatic pancreatic cancer patients.

In the meantime, the company is exploring SCO-101’s potential in other cancer indications, including breast cancer, since preclinical data have shown that SCO-101 can reverse antioestrogen resistance. Last week, the company participated virtually in the San Antonio Breast Cancer Symposium (SABCS), an international conference focused on breast cancer research that runs from December 8-11. On December 9, Scandion Oncology presented its latest preclinical data showing the ability of SCO-101 to re-sensitise antioestrogen resistant breast cancer cells.

»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 of Scandion Oncology

Pursuing clinical validation

Scandion Onocology’s data is promising enough to encourage the company to pursue an evaluation of SCO-101 with antioestrogen resistance in a clinical setting. This summer, Scandion Oncology’s idea for the clinical project received international traction when the company, along with collaborators 2cureX and Erasmus University Medical Center, received a Eurostars grant of 800,000 EUR for bringing the project to life.

The idea behind the project is to have the researchers at Erasmus Medical Center in Rotterdam to perform sophisticated molecular analyses to reveal the molecular mechanisms underlying how SCO-101 counteracts antioestrogen resistance. 2cureX will use the grant to identify patients with the highest likelihood of obtaining clinical benefit from SCO-101 using its IndiTreat Functional Precision Medicine test. This work could lead to a clinical phase Ib study in which women with metastatic breast cancer will be exposed to increasing doses of SCO-101 together with the standard dose of antioestrogens.

CMO and CTO comment on the implications of the project

To learn more about SCO-101’s potential in counteracting antioestrogen resistance, BioStock got in touch with the company’s CMO Peter Michael Vestlev and 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 of 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 of 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.

The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.

 

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