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Tiziana Life Sciences to Launch Spinoff to Market Breast Cancer Recurrence Assay in Europe

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This article has been updated to correct information about a study presented at ASCO. GenomeWeb regrets the error.

NEW YORK – Following the results of a validation study led by researchers at the European Institute of Oncology in Milan, clinical stage pharmaceutical firm Tiziana Life Sciences plans to demerge its genomics-based personalized medicine business into a spinoff company focused on breast cancer recurrence prediction.

London-based Tiziana presented a poster on the study during a session at the virtual American Society of Clinical Oncology meeting last week suggesting that its StemPrintER risk score (SPRS) outperforms Exact Science's Oncotype Dx breast cancer prognostic recurrence assay.

Salvatore Pece, a researcher at the European Institute of Oncology (IEO) who originally developed StemPrintER and the associated SPARE (SPRS for Personalized Adjuvant Therapy in Endocrine Receptor-Expressing Patients) algorithm, explained that his team originally built the platform by profiling mammary stem cells to predict distant metastasis.

Developing a tool based on the biology of the stem cells, the IEO incorporated 20 stem cell genes, as well as four housekeeping genes as part of an RT-qPCR assay. 

"The risk score is a genomic predictor based on the biology of cancer stem cells that predicts recurrence in ER+/HER2- breast cancer cells," Pece explained. "Through StemPrintER, we can interrogate the stem cell biology and measure the 'degree of stemness' of the individual breast cancer."

The process involves preparing a formalin-fixed, paraffin-embedded tissue sample from a breast cancer patient and using Roche's LightCycler 480 instrument to run RT-qPCR on about 200 ng to 250 ng of RNA extracted from the sample. After PCR, the SPARE algorithm establishes a patient's recurrence risk score: below 49 suggests a low risk, between 49 and 59 indicates an intermediate risk, and 59 and above indicates a high risk.

Pece acknowledged that his team would like to improve the platform by using a two-category risk score classifier, "as that's much easier for the physician to use in order to make [therapeutic] decisions." Pece noted that once a patient's biopsy sample arrives at his team's lab, the researchers can provide results to a clinician within a day.

"In other words, the next day after surgery the clinician can assess the risk of recurrence and make decisions … [on whether to] treat the patient with chemotherapy," he noted.

Pece and his colleagues initially published a validation study in The Lancet group's journal, EBioMedicine in 2019 that evaluated the assay's ability to predict distant metastasis risk in a cohort of 2,400 luminal breast patients. While the study suggested that the heterogeneity of breast cancers could be deconvoluted based on the stem-cell concept and guide individualized clinical-decision making in breast cancer patients, Pece noted that that his team downplayed the results because it lacked an independent validation cohort.

The IEO team therefore followed up by further collaborating with colleagues at the Royal Marsden Hospital (RMH) and Queen Mary University (QMU), who independently validated a set of samples from the study's cohort of post-menopausal patients. In the study, presented in a separate ASCO poster, Pece and colleagues analyzed the prognostic value of StemPrintER as an alternate genomic predictor for breast cancer recurrence compared to the Oncotype Dx Recurrence Score (RS) in a cohort of 818 post-menopausal ER+/HER2- breast cancer patients with either negative (629) or one to three positive (189) lymph nodes, treated with anastrozole or tamoxifen.

The RMH and QMU's team assessed the extra prognostic information for distant recurrence risk added by StemPrintER or RS on top of the clinical treatment score (CTS) in the patients treated with the drugs for five years, in a 10-year follow-up period, as well as in the early (0 to 5 years) and late (5 to 10 years) intervals. The CTS — developed by co-author Jack Cuzick and his colleagues at the RMH — is a prognostic risk score that integrates clinical variables to predict late distant recurrence in ER+ breast cancer patients treated with endocrine therapy.

The team found that StemPrintER was an independent predictor of distant metastasis in all patients during the 10-year period when adjusted for clinical parameters expressed by the CTS, as well as in node-negative patients. The group used a predefined StemPrintER cutoff to stratify patients into low- versus high-risk groups, with 454 patients placed in the low-risk group and 364 patients placed in the high-risk group.

Pece and his colleagues also found that StemPrintER outperformed RS in providing prognostic information for 10-year distant metastasis risk in addition to standard clinical parameters, with even greater differences in prediction of late distant metastasis in lymph node-negative patients.

"In terms of biology, StemPrintER is much more accurate than Oncotype Dx likely because StemPrintER has the unique feature to interrogate the intrinsic stemness features of tumors," Pece argued. "In contrast … Oncotype Dx interrogates the very same features of the tumor that are actually considered by the standard clinicopathological parameters, namely estrogen receptor status and proliferation."

Steve Shak, chief medical officer of Exact Sciences, responded in an email that breast cancer physicians aim to use a test to understand whether a patient can clearly derive benefit from chemotherapy.

He believes that the ability of Oncotype Dx — which Exact gained access to last year as part of its acquisition of Genomic Health — to predict chemotherapy benefit continues to distinguish it from other prognostic-only genomic assays. 

"Oncotype DX is the only test that predicts the benefit of chemotherapy in early breast cancer," Shak argued. "Multiple studies have consistently shown large clinically meaningful differences between patient results generated by the Oncotype DX test and other tests, highlighting the risk of under- or overtreating patients if prognostic-only tests are used to make a decision regarding chemotherapy use."

Pece argued that SPARE (which integrates SPRS with lymph nodal status and tumor size in a risk algorithm), is 20% superior to clinical pathological parameters in providing prognostic information in all patients, and from 40% to 50% in lymph node-negative and 1 to 3 lymph node-positive patients, which represent the groups in which the decision making on whether to use or not chemotherapy is the most challenging.

In addition, Pece emphasized that the algorithm's prediction methods are also 40 to 50 percent stronger in node-negative patients and in patients with one to three positive lymph nodes.

However, Pece acknowledged that his team's next goal challenge is extending the validation data to a pre-menopausal patient cohort. The team has therefore established a collaboration with the International Breast Cancer Study Group in Bern, Switzerland, to test the prognostic value of StemPrintER/Spare in about 1,000 patients enrolled in the adjuvant trial, called TEXT, short for Tamoxifen and Exemestane. 

"This will give us a complete representation of all breast cancer patients, as we already know the assay works for both premenopausal and post-menopausal patients from the 2,400-breast cancer patient cohort published in EBioMedicine," Pece said. 

Based on the study's results, Tiziana plans to launch a personalized medicine spinout as a separate publicly traded company on the London Stock Exchange based on the combined StemPrintER and SPARE technology, said Gabriele Cerrone, founder and chairman of Tiziana. Cerrone will serve as chairman of the as-yet-unnamed spinout, while the IEO team will be part of the scientific advisory board.

While the spinout aims to initially offer the assay out of the European Institute of Oncology in 2021, Cerrone believes his team will proceed quickly with expanding the test into the UK and rest of Europe before potentially entering the US market. However, the group is still evaluating which regulatory framework to follow as part of its US plans.

"There is [an] established client base and important local recognition of the institute and the StemPrintER test, which makes Milan a very 'low-hanging' fruit as far as locations with which to launch the test," Cerrone said. "We believe that we can price the test at least 20 percent more competitively than Oncotype Dx."

Cerrone believes that the platform's accuracy is strong enough that several types of patients —including those with negative lymph nodes or a small number of positive lymph nodes — will receive a more personalized treatment. He emphasized that the patients will therefore avoid unnecessary aggressive chemotherapy, as the technology can distinguish patients with sufficiently low risk from higher-risk patients that might benefit from more aggressive treatment.