TMPRSS2

Lynx Dx's Biomarker Test Offers Market-Leading Accuracy in Prostate Cancer Risk Assessment ANN ARBOR, Mich., April 18, 2024 /PRNewswire/ -- Lynx Dx, a leader in innovative diagnostic solutions, hailed new peer-reviewed research published today in the Journal of the American Medical Association (JAMA) Oncology that validates the efficacy of MyProstateScore 2.0 (MPS2), the company's groundbreaking prostate cancer risk assessment test. The findings signify a major advancement in the ability to make highly accurate, comprehensive and personalized predictions by raising the performance standard for urine biomarker tests intended to detect clinically significant prostate cancer. Continue Reading MPS2 (PRNewsfoto/LynxDx) Unmet Need Prostate cancer is the most common cancer and the second leading cause of cancer death in American men, affecting nearly one in eight. The prostate specific antigen (PSA) blood test has long been considered the gold standard for early detection of prostate cancer, but because PSA levels can be elevated for many unrelated reasons, it offers an incomplete picture. Further, more than 75% of men with an elevated PSA will have a biopsy negative for clinically significant cancer. Clinical Validation In the clinical validation of MPS2 published in JAMA Oncology, scientists evaluated whether MPS2 could improve prostate cancer screening outcomes relative to existing biomarkers. Key findings from the paper include: MPS2 was clinically validated separately in patients presenting for initial biopsy (i.e., biopsy naïve) and those presenting for a repeat biopsy (i.e., prior negative biopsy). Use of the test would safely identify 42% to 51% of patients who would not have clinically significant prostate cancer found on biopsy, while maintaining high sensitivity for high-grade cancers. The test was validated for use as a biomarker-only test or inclusive of optional clinical risk factors. The test performed significantly better compared to existing biomarker tests. The research was funded by the Michigan-Vanderbilt Early Detection Research Network Biomarker Characterization Center (grant U2C CA271854) and the Early Detection Research Network Data Management and Coordinating Center (EDRN) (grant U24 CA086368). Study analysis and validation occurred in the EDRN. "The research findings confirm the role of MPS2 to guide a more informed decision about whether to proceed with a prostate biopsy – a decision that is notoriously difficult to get right," said Lynx Dx Chief Medical Officer Spencer Heaton, MD, MBA. "Lynx Dx's goal is to provide best-in-class diagnostic tests that enable urologists and patients to make confident decisions, while greatly improving the rate of life-saving early detection." MPS2 MPS2 is a urine test designed to predict the presence of clinically significant prostate cancer by analyzing expression of 18 unique gene transcripts. The test optimizes diagnostic accuracy for both biopsy naïve patients and those with a prior negative biopsy. Additionally, it provides diagnostic flexibility with optional assessment of personalized risk factors known to influence the development of clinically significant prostate cancer. Lynx Dx has an exclusive license from the University of Michigan to commercialize the groundbreaking science that is the foundation for MPS2. The paper's first authors are Jeffrey J. Tosoian, M.D., M.P.H., who is now at Vanderbilt University, and Yuping Zhang, Ph.D., and Lanbo Xiao, Ph.D., at U-M. Additional authors are Cassie Xie; Nathan L. Samora, M.D.; Yashar S. Niknafs, Ph.D.; Zoey Chopra; Javed Siddiqui; Heng Zheng, M.D.; Grace Herron; Neil Vaishampayan; Hunter S. Robinson, M.D.; Kumaran Arivoli; Bruce J. Trock, Ph.D.; Ashley E. Ross, M.D., Ph.D.; Todd M. Morgan, M.D.; Ganesh S. Palapattu, M.D.; Simpa S. Salami, M.D., M.P.H.; Lakshmi P. Kunju, M.D.; Scott A. Tomlins, M.D., Ph.D.; Lori J. Sokoll, Ph.D.; Daniel W. Chan, Ph.D.; Sudhir Srivastava, Ph.D.; Ziding Feng, Ph.D.; Martin G. Sanda, M.D.; Yingye Zheng, Ph.D. Funding for this work is from the Michigan-Vanderbilt Early Detection Research Network Biomarker Characterization Center and Data Management and Coordinating Center, which are through the National Cancer Institute grants U2C CA271854 and U24 CA086368. Additional funding is from NCI grants P50 CA186786, R35 CA231996, U24 CA115102, U01 CA113913; Prostate Cancer Foundation; Howard Hughes Medical Institute; and the American Cancer Society. Any mention of specific products, services, companies or organizations does not imply endorsement by these organizations. Disclosures: Chinnaiyan serves on the advisory boards of Tempus, Lynx Dx, Ascentage Pharmaceuticals, Medsyn therapeutics, Esanik and RAAPTA therapeutics. Tomlins is an equity holder and chief medical officer of Strata Oncology. Lynx Dx has obtained an exclusive license from the University of Michigan to commercialize MPS2 and the TMPRSS2-ERG gene fusion. Tosoian and Chinnaiyan are equity holders and scientific advisers to Lynx Dx. Siddiqui, Zhang, Xiao and Niknafs have served as scientific advisers to Lynx Dx. Paper cited: "Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer," JAMA Oncology. doi:10.1001/jamaoncol.2024.0455 About Lynx Dx Using technology developed at the University of Michigan, Lynx Dx provides best-in-class diagnostic testing services to help people live healthy and productive lives. The company's mission is to develop superior genomic tests where there is clear patient need. Lynx Dx produces tests with the highest degree of accuracy and efficiency combined with an unparalleled customer experience. For more information about Lynx Dx and MyProstateScore 2.0, please visit . Media Contact Stephanie Fraser [email protected] 734-233-1483 SOURCE LynxDx

Researchers have developed a new urine-based test that addresses a major problem in prostate cancer: how to separate the slow-growing form of the disease unlikely to cause harm from more aggressive cancer that needs immediate treatment. Researchers at the University of Michigan Rogel Cancer Center have developed a new urine-based test that addresses a major problem in prostate cancer: how to separate the slow-growing form of the disease unlikely to cause harm from more aggressive cancer that needs immediate treatment. The test, called MyProstateScore2.0, or MPS2, looks at 18 different genes linked to high-grade prostate cancer. In multiple tests using urine and tissue samples from men with prostate cancer, it successfully identified cancers classified as Gleason 3+4=7 or Grade Group 2 (GG2), or higher. These cancers are more likely to grow and spread compared to Gleason 6 or Grade Group 1 prostate cancers, which are unlikely to spread or cause other impact. More than one-third of prostate cancer diagnoses are this low-grade form. Gleason and Grade Group are both used to classify how aggressive prostate cancer is. Results are published in JAMA Oncology. "Our standard test is lacking in terms of its ability to clearly pick out those who have significant cancer. Twenty years ago, we were looking for any kind of cancer. Now we realize that slow-growing cancer doesn't need to be treated. All of a sudden, the game changed. We went from having to find any cancer to finding only significant cancer," said co-senior study author John T. Wei, M.D., David A. Bloom Professor of Urology at Michigan Medicine. Prostate-specific antigen, or PSA, remains the linchpin of prostate cancer detection. MPS2 improves upon a urine-based test developed by the same U-M team nearly a decade ago, following a landmark discovery of two genes that fuse to cause prostate cancer. The original MPS test, which is used today, looked at PSA, the gene fusion TMPRSS2::ERG, and another marker called PCA3. "There was still an unmet need with the MyProstateScore test and other commercial tests currently available. They were detecting prostate cancer, but in general they were not doing as good a job in detecting high-grade or clinically significant prostate cancer. The impetus for this new test is to address this unmet need," said co-senior author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. Chinnaiyan's lab discovered the T2::ERG gene fusion and developed the initial MPS test. To make MyProstateScore even stronger at identifying high-grade cancers, researchers used RNA sequencing of more than 58,000 genes and narrowed it to 54 candidates uniquely overexpressed specifically in higher-grade cancers. They tested the biomarkers against urine samples collected and stored at U-M through another major study, the National Cancer Institute's Early Detection Research Network. This included about 700 patients from 2008-2020 who came for a prostate biopsy due to an elevated PSA level. This first step narrowed the field to 18 markers that consistently correlated with higher grade disease. The test still includes the original MPS markers, plus 16 additional biomarkers to complement them. From there, the team reached out to the larger Early Detection Research Network (EDRN), a consortium of more than 30 labs across the country that are similarly collecting samples. This ensured a diverse, national sampling. Knowing no specific details about the samples, the U-M team performed MPS2 testing on more than 800 urine samples and sent results back to collaborators at the NCI-EDRN. The NCI-EDRN team assessed MPS2 results against the patient records. MPS2 was shown to be better at identifying GG2 or higher cancers. More importantly, it was nearly 100% correct at ruling out GG1 cancer. "If you're negative on this test, it's almost certain that you don't have aggressive prostate cancer," said Chinnaiyan, S. P. Hicks Endowed Professor of Pathology and professor of urology at Michigan Medicine. Moreover, MPS2 was more effective at helping patients avoid unnecessary biopsies. While 11% of unnecessary biopsies were avoided with PSA testing alone, MPS2 testing would avoid up to 41% of unnecessary biopsies. "Four of 10 men who would have a negative biopsy will have a low risk MPS2 result and can confidently skip a biopsy. If a man has had a biopsy before, the test works even better," Wei explained. For example, a patient may get a prostate biopsy due to an elevated PSA, but no cancer is detected. The patient is followed over time and if his PSA inches up, he would typically need another biopsy. "In those men who have had a biopsy before and are being considered for another biopsy, MPS2 will identify half of those whose repeat biopsy would be negative. Those are practical applications for patients out there. Nobody wants to say sign me up for another biopsy. We are always looking for alternatives and this is it," Wei said. MPS2 is currently available through LynxDx, which is University of Michigan spin-off company that has an exclusive license from the university to commercialize MPS2. Patients interested in learning more can call the Michigan Medicine Cancer AnswerLine at 800-865-1125. The paper's first authors are Jeffrey J. Tosoian, M.D., M.P.H., who is now at Vanderbilt University, and Yuping Zhang, Ph.D., and Lanbo Xiao, Ph.D., at U-M. Additional authors are Cassie Xie; Nathan L. Samora, M.D.; Yashar S. Niknafs, Ph.D.; Zoey Chopra; Javed Siddiqui; Heng Zheng, M.D.; Grace Herron; Neil Vaishampayan; Hunter S. Robinson, M.D.; Kumaran Arivoli; Bruce J. Trock, Ph.D.; Ashley E. Ross, M.D., Ph.D.; Todd M. Morgan, M.D.; Ganesh S. Palapattu, M.D.; Simpa S. Salami, M.D., M.P.H.; Lakshmi P. Kunju, M.D.; Scott A. Tomlins, M.D., Ph.D.; Lori J. Sokoll, Ph.D.; Daniel W. Chan, Ph.D.; Sudhir Srivastava, Ph.D.; Ziding Feng, Ph.D.; Martin G. Sanda, M.D.; Yingye Zheng, Ph.D. Funding for this work is from the Michigan-Vanderbilt Early Detection Research Network Biomarker Characterization Center and Data Management and Coordinating Center, which are through the National Cancer Institute grants U2C CA271854 and U24 CA086368. Additional funding is from NCI grants P50 CA186786, R35 CA231996, U24 CA115102, U01 CA113913; Prostate Cancer Foundation; Howard Hughes Medical Institute; and the American Cancer Society. Disclosures: Chinnaiyan serves on the advisory boards of Tempus, LynxDx, Ascentage Pharmaceuticals, Medsyn therapeutics, Esanik and RAAPTA therapeutics. Tomlins is an equity holder and chief medical officer of Strata Oncology. LynxDx has obtained an exclusive license from the University of Michigan to commercialize MPS2 and the TMPRSS2-ERG gene fusion. Tosoian and Chinnaiyan are equity holders and scientific advisers to LynxDx. Siddiqui, Zhang, Xiao and Niknafs have served as scientific advisers to LynxDx.

New research shows that the recently emerged BA.2.86 omicron subvariant of the virus that causes COVID-19 can be neutralized by bivalent mRNA vaccine-induced antibodies in the blood, which explains why this variant did not cause a widespread surge as previously feared. New research shows that the recently emerged BA.2.86 omicron subvariant of the virus that causes COVID-19 can be neutralized by bivalent mRNA vaccine-induced antibodies in the blood, which explains why this variant did not cause a widespread surge as previously feared. However, the study in cell cultures showed this SARS-CoV-2 variant can infect human cells that line the lower lung and engage in virus-host cell membrane fusion more efficiently, two features linked to severe disease symptoms. The study is published today (Jan. 8, 2024) in the journal Cell. The BA.2.86 variant of omicron is the ancestor of the currently dominating JN.1 and has about 60 more spike protein mutations than the original, or parent, coronavirus, including over 30 more than its close omicron relatives -- the early BA.2 variant and the recently dominant XBB.1.5 variant among them. These mutations led scientists to worry that so many changes would make the variant as tough to contain as the initial omicron outbreak in 2021-22. "We found that, surprisingly, despite all those 60 mutations combined together, BA.2.86 is not as immune-evasive as the XBB.1.5 variant, which until recently had been dominating the pandemic for months. That's good news," said Shan-Lu Liu, senior author the study and a virology professor in the Department of Veterinary Biosciences at The Ohio State University. "But BA.2.86 appears to have increased infectivity of human lung epithelial cells compared to all omicron variants, so that's a little worrisome. And, consistent with infectivity, it also has increased fusion activity with human lung epithelial cells," said Liu, also a professor in the Department of Microbial Infection and Immunity. "That raises a potential concern about whether or not this virus is more pathogenic compared to recent omicron variants." The published findings coincide with reports from the Centers for Disease Control and Prevention that after a brief increase in BA.2.86 infections, its derived sublineage JN.1 rapidly gained ground in the United States, responsible for an estimated 44% of COVID-19 cases as of Dec. 23, 2023. First detected in July in Europe and the Middle East, BA.2.86 and its sublineages have since been spreading with increasing frequency in different parts of the world. On Nov. 22, the World Health Organization classified BA.2.86 and sublineages as "variants of interest." The Ohio State researchers analyzed neutralizing antibodies in blood serum samples from health care professionals who had received three monovalent vaccine doses or two monovalent vaccines followed by one bivalent vaccine booster, and from first responders who had COVID-19 infections during the wave dominated by the XBB.1.5 variant. They compared the ability of neutralizing antibodies to block infection by BA.2.86, an XBB-derived variant known as FLip, the parent virus and several omicron variants. Overall, antibodies produced by serum from the bivalent vaccine-dosed health care professionals were more efficient at neutralizing BA.2.86 than they were at neutralizing other omicron variants, including XBB.1.5. In contrast, the three monovalent vaccines and previous XBB.1.5 infection were barely effective in blocking infection by BA.2.86. "People who have had a COVID-19 infection should remember that omicron variants are less virulent compared to prior variants such as delta, meaning they don't make most people very sick," Liu said. "If you have less severe disease, the antibodies generated by infection are low -- almost 10-fold lower than vaccine-induced antibodies. That is why you cannot rely on natural infection alone for immunity. "While bivalent vaccine can still neutralize BA.2.86, the efficiency is clearly reduced. Therefore, it is important to get the newest booster vaccine, which is formulated with only XBB.1.5 and has been shown to be effective against BA.2.86," Liu added. However, the researchers were surprised to find that a monoclonal antibody known as S309, which has been shown to inhibit almost all other major omicron variants, does not neutralize BA.2.86. Molecular modeling revealed that some of the BA.2.86 mutations in the spike protein might have changed the conformation and rendered S309 unable to neutralize the new variant, Liu said. Additional experiments pointed to the potential for BA.2.86 to be more likely to cause severe disease than its omicron relatives. Researchers found BA.2.86 was more efficient at infecting a cell line derived from the human lower airway epithelium in the lung. Infection of these cells is greatly facilitated through a cell surface protein, known as TMPRSS2, to promote membrane fusion, and this protein is a known contributor to SARS-CoV-2 infection and disease symptoms in the respiratory tract. First author Panke Qu, a graduate student in Liu's lab, conducted the cell-culture studies using pseudoviruses -- a non-infectious viral core surrounded by different SARS-CoV-2 spike proteins on the surface structured to match known variants. "Because we used a pseudovirus, we need to confirm these findings using the real virus," said Liu, also associate director of Ohio State's Center for Retrovirus Research and a program co-director of the Viruses and Emerging Pathogens Program in Ohio State's Infectious Diseases Institute. "But from our past experience, we know that the infectivity in human epithelial cell lines provides very important information. The concern is whether or not this variant, as well as its descendants including JN.1, will have an increased tendency to infect human lung epithelial cells similar to the parental virus that launched the pandemic in 2020." Liu noted that other labs have recently suggested that JN.1, one of fastest-growing descendants of BA.2.86, is much more resistant to neutralizing antibodies that are effective against BA.2.86. "We know that coronaviruses are prone to viral recombination, which can lead to new variants with huge numbers of mutations that could have increased immune evasion but also disease severity," he said. "That's why surveillance of the variants is still very important, even though we are in the end of year four of the pandemic." This work was supported by anonymous donor funds, the National Institutes of Health, the National Center for Advancing Translational Sciences, the Glenn Barber Fellowship from Ohio State's College of Veterinary Medicine, the Robert J. Anthony Fund for Cardiovascular Research, and Ohio State's Comprehensive Cancer Center and Center for Clinical and Translational Science. Additional co-authors, all from Ohio State, are Kai Xu, Julia Faraone, Negin Goodarzi, Yi-Min Zheng, Claire Carlin, Joseph Bednash, Jeffrey Horowitz, Rama Mallampalli, Linda Saif, Eugene Oltz, Daniel Jones and Richard Gumina.