Rna
Dna
Differences
SeveridiaTM

SeveridiaTM
Measurement of RDD rates to Determine Cancer Severity

GENCLIS is the only biotechnology company to exploit the measurement of levels of RNA-DNA differences and the nature of these differences to create new tools for predictive medicine.

Our scope is mainly directed towards oncology. Our first goal is to characterize the severity of each cancer type, which will enable the therapeutic strategy to be tailored to the needs of each patient.

To achieve this goal, we focus on oncologists’ needs by considering discrepancies between patients who carry the same type of cancer but have very different clinical outcomes.

We have shown that there is a strong association between RDD levels and severity within the same cancer type, as well as between different severe and non-severe cancer types.

This discovery allows us to propose, in line with the medical needs of oncologists, tests for predicting the severity of several cancers.

SeveridiaTM TNBC

Triple-negative breast cancer (TNBC) refers to infrequent but severe forms of breast cancer that express none of the following three pathological markers: estrogen receptor (ER), progesterone receptor (PR), or HER2/Neu receptor (ERBB2).

TNBC is characterized by the absence of ER and PR expression and ERBB2 overexpression.

TNBC affects over 150,000 women and causes more than 50,000 deaths worldwide every year. This cancer type is responsible for approximately 75,000 to 100,000 treatments by adjuvant chemotherapy (after surgery).
TNBC accounts for 15% to 25% of all breast cancers and is most often found in young women of African-American or Hispanic origin.

Although about 95% of TNBCs are nonmetastatic, TNBC is responsible for 35% of breast cancer-related deaths.

Clinical characteristics of TNBC have important consequences :

  • Hormone therapy-based breast cancer treatments targeting ER, PR (Tamoxifen), or ERBB2 (Herceptin) cannot be used for TNBC. Consequently, TNBC treatment is based on conventional chemotherapies, which are relatively less costly but have considerably more severe side effects.
  • Two thirds of women with nonmetastatic TNBC are cured after surgical intervention and will require no further treatment. However, one third of patients evolve unfavorably within 2 to 5 years, despite conventional chemotherapy, which improves the probability of survival by 40%.

The SeveridiaTM TNBC test allows separation of TNBC patients into two groups, corresponding to survival: i.e., a good outcome group and a poor outcome group.

TNBC3

By measuring the RDD levels in data generated by Next Generation Sequencing (Illumina) and a proprietary algorithm, the SeveridiaTM TNBC test establishes a score. Above a defined threshold, this score predicts a good outcome. Below this score, patients are classified in the poor outcome group. The test was established with 20 patients and subsequently replicated in a blinded manner in 57 patients. All 77 patients were recruited at 13 different centers, located in Europe and the United States.

score_TNBC2
The SeveridiaTM score was calculated on 77 patients : 20 for training set (blue and red ) and 57 for the 4 validation sets.

A representation of the probability of survival of these 57 patients is used to demonstrate the effectiveness of the SeveridiaTM TNBC test.

km_1ckm_2c

Patients classified into the good outcome group have a 100% probability of survival at 2,500 days, whereas patients classified into the poor outcome group have only a 34% probability of survival at 2,500 days.

The SeveridiaTM TNBC test is intended for a very specific market, representing 20% of breast cancers for which competitive tests do not exist.

SeveridiaTM testing process:

  • 1
    A patient is diagnosed with breast cancer.
  • 2
    The tumor is not metastatic and is characterized as triple negative by anatomic and pathological examination.
  • 3
    RNA sequences are generated from tumor tissue.
  • 4
    RNA sequences are aligned against the human reference genome.
  • 5
    Alignments are analyzed by using algorithms developed by GENCLIS.
  • 6
    The SeveridiaTM score allows patients to be separated into two groups: a good outcome group and a poor outcome group.
    Patients in the first group should not receive chemotherapy, but would benefit from close monitoring. Patients in the second group should receive adjuvant therapy and may be good candidates for new treatments targeting the immune system or tumor cells. SeveridiaTM is not yet ready for commercial marketing, but will be, once independent blinded studies (ongoing) are replicated.