ADAM12

Immunotherapy Response Score predicts rwPFS and OS across tumor types Presents opportunity to expand immunotherapy benefit to more patients and optimize use ANN ARBOR, Mich., Feb. 7, 2023 /PRNewswire/ -- Strata Oncology, Inc., a next-generation precision oncology company enabling smarter and earlier cancer treatment, today announced the publication of a new peer-reviewed study validating the clinical utility of the company's proprietary pan-solid tumor predictive biomarker for anti-PD-1/PD-L1 checkpoint inhibitor monotherapy benefit, Immunotherapy Response Score (IRS). The study was published by Communications Medicine, a Nature publication. Strata Oncology developed IRS using treatment data and comprehensive, clinically validated genomic and transcriptomic profiling of tumor tissue from the Strata Trial®, an ongoing observational clinical trial evaluating the impact of molecular profiling for patients with advanced solid tumors. The biomarker algorithm, which was validated in an independent cohort of trial patients, captures the biology of the tumor and its microenvironment by combining tumor mutation burden (TMB) with quantitative expression of PD-L1, PD-1, ADAM12 and TOP2A. "Our Immunotherapy Response Score meets a significant unmet medical need for an integrative diagnostic test that better predicts likelihood of benefit from anti-PD-1/PD-L1 checkpoint inhibitor monotherapy, across solid tumor types," said Scott Tomlins, M.D., Ph.D., Strata Oncology co-founder and Chief Medical Officer. "Current pan-tumor biomarkers for these treatments identify only a fraction of responsive patients, meaning far too many people who could benefit from these therapies are not being identified." Tomlins continued: "Additionally, immunotherapy is now often combined with chemotherapy. Our exploratory data in non-small cell lung cancer indicate that IRS may be a useful tool to help determine which patients can achieve similar benefit without the toxic effects of chemotherapy." Key findings from the study include: IRS predicted real-world progression-free survival and overall survival in anti-PD-1/PD-L1 monotherapy treated patients across tumor types IRS-high status predicted similar duration of benefit as tumor mutational burden (TMB)-high status across tumor types, but identified twice as many patients who may benefit from checkpoint inhibitor treatment as TMB In non-small cell lung cancer (NSCLC) patients who were IRS-high, there was no significant benefit of combination therapy (pembrolizumab + chemotherapy) compared to monotherapy (pembrolizumab) "Immunotherapy has transformed cancer care and now with IRS we have the ability to predict benefit across tumor types," said Dan Rhodes, Ph.D., Strata Oncology co-founder and Chief Executive Officer. "We are excited to put this novel biomarker into the hands of physicians to help them ensure every patient gets their best possible therapy." About Strata Oncology Strata Oncology, Inc. is a precision oncology company dedicated to delivering the best possible treatment for each patient with cancer. The company combines molecular profiling, real-world data, and a large-scale clinical trial platform to identify and deliver optimal treatments for patients with cancer. For more information visit strataoncology.com. Media Inquiries: Rachel Ford Hutman [email protected] +1 (301) 801 5540 SOURCE Strata Oncology, Inc.

Chronic diseases often lead to fibrosis, a condition in which organ tissue suffers from excessive scarring. Researchers have now developed an immunotherapy that specifically targets the cause -- activated fibroblasts -- while leaving normal connective tissue cells unharmed. If this approach is also found to work in humans, it could lead to an effective treatment for fibrosis. Fibrosis is a pathological proliferation of connective tissue that destroys the organ tissue. It is the ultimate consequence of almost every kind of chronic damage. Fibrosis can occur in almost every type of tissue in the body, although the liver, lungs, heart and kidneys are most often affected. Fibrosis is responsible for up to 45 percent of all mortality in industrialized countries. Inflammation or vascular disorders often cause chronic organ damage. They activate the fibroblasts, which then begin to proliferate uncontrollably and create deposits of fibrous tissue. This scars the organ tissue, destroying it little by little. The functioning of the affected organ worsens noticeably until it fails completely. Eliminating activated fibroblasts while leaving resting cells undamaged An international research team led by the University of Zurich (UZH) has now developed a new strategy to eliminate fibroblasts in a targeted manner. "In animals, we were able to trigger an immune response similar to that to a vaccination, in which the activated connective tissue cells were destroyed while the resting fibroblasts were left unharmed," explains study leader Professor Christian Stockmann of the Institute of Anatomy at the University of Zurich. In this manner, researchers were able to reduce fibrosis in vital organs such as liver and lungs while at the same time leaving healthy tissue unharmed. Difference in surface structures identified This is where previous strategies for fibrosis treatment had previously failed, since they also damaged resting fibroblasts. Resting fibroblasts are important, however, for maintaining the structure and functioning of healthy tissue. Researchers therefore studied the differences between the surfaces of resting and of activated connective tissue cells. "Our computer-assisted analyses revealed that fragments of two surface proteins -- Adam12 and Gli1 -- which can be detected by the immune system, are present in large numbers on activated fibroblasts, while there are very few on the resting cells," explains Stockmann. The activity of these two protein genes is stimulated by chronic tissue damage, which means the activated fibroblasts produce the said proteins in larger quantities. Immunotherapy reduces lung and liver fibrosis in mice The researchers then used these two surface structures as a vaccine in mice in order to trigger an immune response via cytotoxic T-cells. These immune cells normally eliminate virus-infected or cancerous cells. "With the newly developed immunotherapy, we were able to eliminate fibroblasts efficiently in mice, thus reducing fibrosis in the liver and the lungs, without affecting healthy organ tissue," says Stockmann. If scientists manage to successfully trigger a comparable, targeted immune response in humans, then vaccine-based immunotherapy could be used in future for the treatment of patients with organ fibrosis.