Proxeom is an early stage company, that is developing ultra-sensitive non-invasive liquid biopsy based nucleic acid assay technologies for detecting organ transplant rejection, presence and persistence of tumors and host response to disease.


Liquid biopsy: A whole body survey for presence of a disease

The term "liquid biopsy" has been coined as a contrast with "tissue biopsy". In liquid biopsy, blood or body fluids are used to query the disease state of the body. Blood, through its network of capillaries, makes contact with all cells in the body and can therefore collect materials ejected by normal and diseased cells. By detecting the presence of disease markers in blood it then become possible to detect a disease state even without knowing the exact location of the diseased tissue. 
Liquid biopsy is likely to impact many areas of healthcare, such as the impact of infectious agents on host response, inflammatory disease foci, host response to tissue transplanatation and to the detection and monitoring of cancer.

Liquid biopsy is expected to revolutionize cancer Dx by supplementing tissue biopsy to determine prognosis and therapeutic regimens.
Presence of mutations in the blood stream or in body fluids would enable early detection of a tumor as-well-as post-diagnostic monitoring and prediction of a relapse.

The following attributes make detection of nucleic acid based markers through liquid biopsy compelling:
  • Lower cost - reduces the need for surgical procedures and the costs of tissue processing, staining, and analysis
  • Non-invasive - reduces the need to locate and then sample a tumor to perform diagnostic tests
  • Definitive diagnosis - genomic lesions likely to provide more definitive indications
  • Continuous monitoring - ease of non-invasive sampling allows the disease status to be monitored over extended time periods
  • Detecting tumor heterogeneity - diagnosis and treatment often depends on an assumption that the sample aliquot is representative of the whole tumor. Liquid biopsy tends to be more inclusive though dominant genomic lesions are more likely to be detected.
  • Detecting clonal change - changes in the clonal cell population, for example, from a treatment susceptible clone to a resistant clonal population is more easily detected by liquid biopsy approaches. 

Liquid biopsy requires highly-sensitive detection methods

The primary challenge for the detection of circulating cell-free nucleic acid markers in blood and body fluids is in detecting the low amounts present in the large pool of normal circulating cell-free nucleic acids. Current detection limits of quantitative Polymerase Chain Reaction (qPCR) and of Next Generation Sequencing (NGS) based approaches are not adequate to detect the low amounts of the disease marker. 

Modifications on the core qPCR methods, for example by using Locked Nucleic Acid primers or by the development of counting approaches such as digital PCR alleviate some of the challenges with qPCR but still require a priori knowledge of the specific genetic change that is to be detected so that an assay can be designed and optimized. For highly dynamic diseases such as cancer, where the mutation profile changes with time, PCR based assays are difficult to implement.

Next Generation Sequencing based approaches, which query genes or regions rather than mutations, are better suited to changing diseases such as cancer, as new mutations can be detected as they appear. The detection limits for Next Generation Sequencing workflows are ~1% or higher for adequate sensitivity and specificity. That is, if a mutation is present in a normal pool of DNA at lower than 1%, it may not be detected by Next Generation Sequencing. Approaches that label individual DNA molecules with a unique DNA barcode can improve the detection limit by a factor of 10 but at the cost of over-sequencing. Most unique barcode based approaches require sequencing depths of 10,000x to 50,000x for the the error correction to be implemented.

Proxeom's solution to highly-sensitive detection

At Proxeom we are developing solutions for liquid biopsy applications using Next Generation Sequencing, which are expected to deliver limits of detection of 0.01-0.1% with high sensitivity and specificity at sequencing depths of approximately 2,000-5,000x which will improve the true detection rate at a lower sequencing cost. 

Please, check the technology section where we will release more information as the patent filing process progresses.
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