MammaTyper® Enables More Precise Prediction of the Response to Neoadjuvant Chemotherapy Compared to

First comparison of a biomarker analysis by RT-qPCR (MammaTyper®) versus visual or computer-assisted immunohistochemistry (IHC) in subtyping mammary carcinomas

• Significantly more precise prediction of pathologically complete remission in a neoadjuvant setting with MammaTyper® compared to manual or computer-assisted IHC; better therapy stratification and possible avoidance of unnecessary therapies
• MammaTyper® provides reliable quantitative determination of MKI67-mRNA expression

BioNTech Diagnostics GmbH, a subsidiary of BioNTech AG, announces the publication of further study data which again document the superiority of the in-vitro diagnostic MammaTyper® test (CE marked IVD) over immunohistochemical detection methods (IHC) (1). "The special feature of the currently published performance evaluation study is the fact that, for the first time, results of gene expression analysis with MammaTyper® were not only compared with results of manual microscopic analysis of immunohistochemical specimens but also with computer-assisted image analysis", emphasized Dr. Sierk Pötting, Managing Director of BioNTech Diagnostics GmbH. The study used formalin-fixed, paraffin-embedded (FFPE) routine biopsy samples from breast cancer patients who had participated in a randomized neoadjuvant study (2). These samples were analyzed with the three methods prospectively and retrospectively. In the currently published study, as well as in previous publications (3,4), MammaTyper® demonstrated a significant superiority in the quantitative determination of the proliferation marker MKI67 (Ki-67) compared to IHC. Therefore MammaTyper® achieves significantly higher specificity than IHC in the identification of a possible pathological complete remission after neoadjuvant therapy. Prof. Dr. Hans-Peter Sinn, University of Heidelberg and head of the study summarized the results as follows: "The study demonstrates that MammaTyper® is able to reliably prognosticate tumor proliferation activity and the response to neoadjuvant therapy. That means patients may be spared unnecessary treatments".

The classification of tumors in luminal, basal and HER2-amplified subtypes by the immunohistochemical markers estrogen receptor (ER), progesterone receptor (PR), HER2 and the proliferation marker Ki-67 provides the basis of biological subtyping and (neo)adjuvant therapy decisions for mammary carcinomas (5). Moreover, since the 2013 St Gallen Conference, the proliferation marker Ki-67 has also been confirmed for the definition of the intrinsic subtypes Luminal A and Luminal B-like (6). An earlier study in a neoadjuvant setting was able to show that high Ki-67 values are consistently associated with higher rates of pathological complete remission (11). The current standard method for detection of the Ki-67 proliferation marker as well as the biomarkers ER and PR is manual microscopic immunohistochemistry which has, however, been debated for some time due to the great intra- and inter-observer variability (7,8).

Results of the determination of biomarkers ESR1 (ER) and PGR (PR) in the currently published study again confirm the good correlation of MammaTyper® with immunohistochemistry results, showing a slightly higher correlation of MammaTyper® and computer-assisted immunohistochemistry (ER/ESR1: 91.23 %, p<0.0001; PR/PGR: 92.9 %, p < 0.0001). In contrast, MammaTyper® and computer-assisted IHC image analysis achieved , as expected, moderate correlation (Spearman’s r = 0.5; p = 0.0001) in the detection of the proliferation marker MKI67 (Ki-67). However, correlated with clinical progress data, MammaTyper® proved to be significantly superior to IHC – especially in predicting the response to neoadjuvant therapy derived from MKI67 determination.

The current study shows again that MammaTyper® is an interesting and reliable alternative to the currently customary IHC detection methods. Moreover, MammaTyper® offers the possibility  for an improved prediction of pathological complete remission after neoadjuvant chemotherapy.
Therefore, MammaTyper® could contribute to a well-founded therapy decision which could spare breast cancer patients unecessary treatments in the future.

About MammaTyper®
MammaTyper® is a molecular in vitro diagnostic test for quantitative detection of the mRNA expression status of the genes ERBB2 (HER2), ESR1 (ER), PGR (PR) and of MKI67 (proliferation marker Ki-67) in the tumour tissue of female patients with newly diagnosed invasive breast cancer. The test has been validated for total RNA extracted from tissue specimens or biopsies.

MammaTyper® is used for molecular subtyping of breast cancer tissue according to the St Gallen classification (2013) in luminal A-like, luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive (non-luminal) and triple negative (ductal) tumours, and offers together with further clinical pathological factors the possibility of significantly improving the diagnostic and the treatment of female patients with breast cancer. The test can be carried out in any pathology laboratory. MammaTyper® can be used on all female patients with newly diagnosed invasive breast cancer and provides the results on the same day. With MammaTyper®, BioNTech underlines its commitment to making personalized medicine generally available in the field of cancer treatment.

About BioNTech Group
BioNTech Group, consisting of BioNTech AG and its subsidiaries, is an immunotherapy leader with bench-to-market capabilities, developing truly personalized, well-tolerated and potent treatments for cancer and other diseases. Established by clinicians and scientists the Group is pioneering disruptive technologies ranging from individualized mRNA based medicines through innovative Chimeric Antigen Receptors /T-cell Receptor-based products and novel antibody checkpoint immunomodulators. BioNTech’s clinical programs are supported by an in-house molecular diagnostics unit whose products include MammaTyper^® a molecular in-vitro diagnostic kit, marketed as IVD under CE marking in the European Union (and Switzerland) and in certain other countries. Founded in 2008, BioNTech is privately held, with Strüngmann Family Office as a majority shareholder, having closed the largest initial financing in the European biopharma sector’s history.

About BioNTech Diagnostics GmbH
BioNTech Diagnostics is a fully-owned subsidiary company of BioNTech AG. The ISO 9001/13485 certified company has extensive product and service offerings ranging from biomarker discovery and validation through molecular screening assays, patient stratification and companion diagnostics to clinical monitoring, all to international regulatory standards. Early detection of diseases that have a high mortality rate and the appropriate selection of therapies are crucial for a successful treatment of patients. BioNTech Diagnostics’ mission is to provide new and innovative diagnostic tests to extend lives of patients, improve their quality of life and support the use of appropriate therapy for each individual patient.