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Study cites major accuracy flaws in predominant liquid biopsy platforms offered by competitors

NEW HAVEN, CT, (April 03rd, 2018) – Specialty cancer diagnostics company Precipio, Inc. (NASDAQ: PRPO), announced today that, in response to recent articles, its approach using ICE COLD-PCR™ liquid biopsy tests on Real-Time PCR (RT-PCR) platforms enables laboratories validating and developing these tests internally to produce consistent and reproducible results.1

Accuracy of NGS-based liquid biopsy tests questioned

A recent article published in the JAMA Oncology Journal revealed alarming inconsistencies in results generated by two leading liquid biopsy competitors. In only 3 of 40 patient samples sent in parallel to two CLIA & CAP certified laboratories, were the same results reached and reported.2

This is mainly a result of these tests conducted on Next-Generation Sequencing (NGS) platforms, which create a challenge to generate consistent results in different laboratories.3 NGS platforms require the internal development of bioinformatics pipelines and DNA libraries that are used to analyze large data sets, and are then interpreted by highly specialized bio-informaticians.4

Since these bioinformatics pipelines are not standardized, this can cause inconsistencies from one facility to another, as demonstrated in this recent study. Additionally, due to the volume and complexity of data generated by NGS, the interpretation of the data is dependent on the analysis of highly trained bio-informatic scientist as well as a review and interpretation by a molecular pathologist (or a board certified PhD-level lab director).

Limit of Detection (LOD) a key factor

One of the reasons laboratories have selected NGS platforms to conduct liquid biopsy testing is due to the detection limits of other platforms, such as RT-PCR. While RT-PCR platforms can typically reach an LOD of 5-10%, NGS platforms are able to reach an LOD of 3-5%. This is significant because these platforms were initially designed to detect genetic mutation taken from actual tumor (solid) biopsy samples, where the tumor DNA concentration is typically 10% or higher.

With the advent of liquid biopsies – blood samples that have diminutive fragments of DNA within a sample (often less than 1% of the sample DNA) – the sensitivity of these platforms was often insufficient to detect those DNA fragments within a sample of blood.

Using multiple repeat-testing cycles which achieves a reduction (improvement) in their LOD, laboratories using NGS were able to reduce its LOD to as low as 0.1%, thus enabling them to detect tumor DNA within blood samples. However, this also caused some of the complexities described above, resulting in inconsistent outcomes.

ICP-enabled RT-PCR platform selected to ensure consistent results

Precipio’s proprietary ICE-COLD PCR™ mutation enrichment technology is highly flexible and can be run on multiple platforms, among them RT-PCR, which offers a standardized and consistent approach through a focused search for clinically relevant mutations, showing a snapshot of the patient’s current status. It requires no internally-developed processes; rather, it merely requires the following of pre-determined, manufacturer-set protocols.

RT-PCR platforms typically have an LOD of 5-10%. However, coupled with Precipio’s ICE-COLD PCR’s mutation enrichment technology, RT-PCR can surpass mutation detection levels achievable by NGS using a single run, and result in LODs as low as 0.1%. This is a groundbreaking advance for RT-PCR platforms, and effectively propels this platform into the field of liquid biopsy testing, which is otherwise (absent the incorporation of ICP) outside of the required LOD range for liquid biopsies.

The combination of ICP on a RT-PCR platform creates a liquid biopsy testing platform that is standardized, consistent and simpler, producing reliable results that do not require complex laboratory developed bio-informatic pipelines and highly trained scientists for a subjective evaluation.

Coupled with the recent incorporation of Heat Resolution Melt (HRM) technology, Precipio’s liquid biopsy test reagents are the only ones available in the market that not only rule out samples that are negative for the mutations of interest up front, but also allow downstream mutation detection by real-time PCR without the uncertainty of accuracy associated with next generation sequencing (NGS).

Future ICP Product Developments will include NGS

Despite the challenges of NGS described above, part of Precipio’s 2018 development plans include the adaptation of ICP to NGS platforms. However, we plan to address those challenges by developing our own bioinformatics pipeline and DNA libraries, and making those accessible to all ICP platform users who chose to implement it on NGS.

These pre-developed libraries will eliminate the variability inherent in each laboratory setting up their own NGS libraries. A subsequent benefit of this shared pipeline will be the increased robustness and precision resulting from a large number of users generating data to continuously refine the library.

A critical part of our product development plan was to ensure that laboratories implementing ICP will deliver consistent results to their physicians and their patients. We believe that in order to create a product that can enable a true LDT (Laboratory Developed Test) in any laboratory, it was imperative to preserve the reliability, consistency and reproducibility of liquid biopsy test results, ensuring that the accuracy of our results would never be called into question.

About Precipio

Precipio has built a platform designed to eradicate the problem of misdiagnosis by harnessing the intellect, expertise and technology developed within academic institutions and delivering quality diagnostic information to physicians and their patients worldwide. Through its collaborations with world-class academic institutions specializing in cancer research, diagnostics and treatment such as the Yale School of Medicine and Harvard’s Dana-Farber Cancer Institute, Precipio offers a new standard of diagnostic accuracy enabling the highest level of patient care. For more information, please visit www.www.precipiodx.com.

Forward-Looking Statements

Certain statements in this press release constitute “forward-looking statements,” within the meaning of federal securities laws, including statements related to ICP technology, including financial projections related thereto and potential market opportunity, plans and prospects and other statements containing the words “anticipate,” “intend,” “may,” “plan,” “predict,” “will,” “would,” “could,” “should,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The Company’s actual results could differ materially from those anticipated in these forward-looking statements as a result of various factors. Factors that could cause future results to materially differ from the recent results or those projected in forward-looking statements include the known risks, uncertainties and other factors described in the Company’s definitive proxy statement filed on May 12, 2017, the Company’s Quarterly Reports on Form 10-Q for the quarters ended June 30, 2017 and September 30, 2017, the Company’s prior filings and from time to time in the Company’s subsequent filings with the Securities and Exchange Commission. Any change in such factors, risks and uncertainties may cause the actual results, events and performance to differ materially from those referred to in such statements. All information in this press release is as of the date of the release and the Company does not undertake any duty to update this information, including any forward-looking statements, unless required by law.

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1Clin Chem.2009 Apr;55(4):611-22. doi: 10.1373/clinchem.2008.112797. Epub 2009 Feb 26.
2Schlingman, JD. “Johns Hopkins University Study Finds Laboratory-Developed Liquid Biopsy Tests Can Give Different Results; Call for ‘Improved Certification’ of Medical Laboratories That Develop These LDTs.” www.darkdaily.com, 2, Mar. 2018.
3Ratner, Mark. “Jury out on Liquid Biopsies for Cancer.” www.nature.com, 1 Mar. 2018.
4AMA Magi A, Benelli M, Gozzini A, Girolami F, Torricelli F, Brandi ML. Bioinformatics for Next Generation Sequencing Data. Genes. 2010;1(2):294-307. doi:10.3390/genes1020294.