ACC1

Researchers used Standard BioTools’ high-content SomaScan® Platform and SomaSignal™ tests for MASH/NASH to identify 69 blood biomarkers that correlate with clinical measures of liver diseaseSOUTH SAN FRANCISCO, Calif., Sept. 18, 2024 (GLOBE NEWSWIRE) -- Standard BioTools Inc. (Nasdaq:LAB) today announced a recent paper published in Nature Scientific Reports, by researchers at Pfizer Research and Development, that detailed their use of the high-plex SomaScan® Assay, leveraging an industry-leading 7,000-protein biomarker panel to analyze blood serum samples from patients in a Phase 2a clinical trial for nonalcoholic fatty liver disease (NAFLD) and NASH. Nonalcoholic Fatty Liver Disease, or NAFLD, and nonalcoholic steatohepatitis (NASH) are becoming a global population health concern. Because diagnosing these diseases involves invasive liver biopsies, which can be challenging and expensive, many patients go untested and untreated. These diseases are complex in their impact on the liver, creating lipid accumulations, stiffness in the liver tissue, ballooning of the liver and chronic inflammation. In collaboration with major pharmaceutical companies and leading academic centers, SomaLogic (now Standard BioTools) previously developed serum proteomic SomaSignal™ tests which correlate more faithfully with each component of the liver biopsy than any other noninvasive biomarkers. Because these tests run on the full SomaScan® Platform, covering thousands of protein measurements, the study’s researchers were able to infer liver biopsy effects and identify additional mechanistic pharmacodynamic protein biomarkers to characterize their drug mechanism and measure response in clinical trials. “NASH and NAFLD are a significant challenge in terms of diagnosis and treatment, and the prevalence of metabolic and obesity-related diseases around the world has created a strong sense of urgency to learn more about them and find better ways of treating them,” said Standard BioTools Chief Medical Officer Stephen A. Williams, MD, PhD. “The SomaScan Assay gives us a view of the biological mechanisms of this disease with a simple blood draw from patients, and SomaSignal tests were shown in this study to be valuable in showing disease regression in patients.” The study focused on inhibiting the protein ACC1 using clesacostat, a drug that acts as an acetyl-CoA carboxylase inhibitor. Using the SomaScan Assay, researchers found 69 blood analytes that strongly correlated with clinical measures of liver inflammation and steatosis. They also discovered the expression of these analytes was significantly higher in NASH patients compared to their NAFLD counterparts. Additionally, in 231 patients in the pre-treatment phase, Standard BioTools’ SomaSignal tests were used to measure 37 different analytes that correlate with NASH and NAFLD. The tests helped researchers stratify patients by disease severity, establish a pre-treatment baseline, and monitor the effects of the drug. The 37 analytes were identified by screening thousands of patient samples using the SomaScan Assay. These analytes were shown to have critical differences in NASH and NAFLD patients and were validated against standard clinical measurements. During the 16-week trial, the SomaScan assay and SomaSignal tests were run on serum samples from study participants subjected to a once-per-day dose of clesacostat. The SomaSignal test scores aligned with improvements in liver fat content (steatosis) as measured by proton density fat fraction, or MRI-PDFF. Twenty-seven analytes were found to be significantly reversed upon drug treatment, demonstrating the utility of SomaSignal tests for classification of NASH and the ACC inhibition treatment-induced effects on steatosis. “The SomaScan Platform has been extensively and systematically validated, providing a strong foundation for this important research,” said Michael Egholm, PhD, President and Chief Executive Officer of Standard BioTools. “These researchers also used the powerful SomaSignal tests to better diagnose NASH and NAFLD patients and to study their responses to treatment.” Standard BioTools now offers the new SomaScan 11K Assay, as well as the industry leading single cell proteomics and spatial proteomics solutions (CyTOF® and Hyperion™ platforms), as a comprehensive pharma services offering to customers who are working to identify biomarkers of predictive response, mechanism of action and patient stratification in their studies. About Standard BioTools Inc. Standard BioTools Inc. (Nasdaq:LAB), the parent company of SomaLogic Inc. and previously known as Fluidigm Corporation, is driven by a bold purpose – Unleashing tools to accelerate breakthroughs in human health. Standard BioTools has an established portfolio of essential, standardized next-generation technologies that help biomedical researchers develop medicines faster and better. As a leading solutions provider, the company provides reliable and repeatable insights in health and disease using its proprietary mass cytometry and microfluidics technologies, which help transform scientific discoveries into better patient outcomes. Standard BioTools works with leading academic, government, pharmaceutical, biotechnology, plant and animal research and clinical laboratories worldwide, focusing on the most pressing needs in translational and clinical research, including oncology, immunology and immunotherapy. Learn more at standardbio.com or connect with us on X, Facebook®, LinkedIn and YouTube™. For Research Use Only. Not for use in diagnostic procedures. Limited Use Label License and other terms may apply: www.standardbio.com/legal/salesterms. Patent and License Information: www.standardbio.com/legal/notices. Trademarks: www.standardbio.com/legal/trademarks. Any other trademarks are the sole property of their respective owners. ©2024 Standard BioTools Inc. (f.k.a. Fluidigm Corporation). All rights reserved. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, among others, statements regarding future financial and business performance; expectations, operational and strategic plans; the merger of the Company and SomaLogic; deployment of capital; market and growth opportunity and potential; and the potential to realize the expected benefits following the merger of the Company and SomaLogic. Forward-looking statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from currently anticipated results, including, but not limited to, the outcome of any legal proceedings related to the merger; risks that the anticipated benefits of the merger or other commercial opportunities may otherwise not be fully realized or may take longer to realize than expected; risks that we may not realize expected cost savings from our restructuring, including the anticipated decrease in operational expenses, at the levels we expect; possible restructuring and transition-related disruption, including through the loss of customers, suppliers, and employees and adverse impacts on our development activities and results of operation; restructuring activities, including our subleasing plans, customer and employee relations, management distraction, and reduced operating performance; risks that internal and external costs required for ongoing and planned activities may be higher than expected, which may cause us to use cash more quickly than we expect or change or curtail some of our plans, or both; risks that our expectations as to expenses, cash usage, and cash needs may prove not to be correct for other reasons such as changes in plans or actual events being different than our assumptions; changes in Standard BioTools’ business or external market conditions; challenges inherent in developing, manufacturing, launching, marketing, and selling new products; interruptions or delays in the supply of components or materials for, or manufacturing of, Standard BioTools products; reliance on sales of capital equipment for a significant proportion of revenues in each quarter; seasonal variations in customer operations; unanticipated increases in costs or expenses; uncertainties in contractual relationships; reductions in research and development spending or changes in budget priorities by customers; uncertainties relating to Standard BioTools’ research and development activities, and distribution plans and capabilities; potential product performance and quality issues; risks associated with international operations; intellectual property risks; and competition. For information regarding other related risks, see the “Risk Factors” section of Standard BioTools’ most recent quarterly report on Form 10-Q filed with the U.S. Securities and Exchange Commission (the “SEC”) on November 7, 2023, on its most recent annual report on Form 10-K filed with the SEC on March 14, 2023, and in Standard BioTools’ other filings with the SEC, as well as the “Risk Factors” section of SomaLogic’s most recent quarterly report on Form 10-Q filed with the SEC on November 8, 2023, on its most recent annual report on Form 10-K filed with the SEC on March 28, 2023, and in SomaLogic’s other filings with the SEC. These forward-looking statements speak only as of the date hereof. Standard BioTools disclaims any obligation to update these forward-looking statements except as may be required by law. Media ContactEmilia Costales720 798 5054emilia.costales@standardbio.com Investors David Holmesir@standardbio.com

Various conditions such as postpartum depression or postpartum psychosis can lead to an alteration in maternal behavior and disrupt the mother-child bonding process. A research team has conducted a study in which they were able to identify the neuronal circuits in the brain that are activated during the learning of maternal behavior. The findings can serve as a basis for developing therapeutic interventions. Various conditions such as postpartum depression or postpartum psychosis can lead to an alteration in maternal behaviour and disrupt the mother-child bonding process. A research team led by Daniela Pollak from MedUni Vienna's Center for Physiology and Pharmacology has conducted a study in which they were able to identify the neuronal circuits in the brain that are activated during the learning of maternal behaviour. The findings, published in The EMBO Journal, can serve as a basis for developing therapeutic interventions. In the course of their preclinical investigation, the scientists led by Daniela Pollak from the Division of Neurophysiology and Neuropharmacology at MedUni Vienna's Center for Physiology and Pharmacology analysed maternal behaviour of female mice towards newborn pups. While the neural processes involved in the development of maternal care behaviour in female mice after birth have already been described, the current study addressed the question which circuits in the brain are activated during the learning of care behaviour in nulliparous virgin females, female mice that have not been pregnant. The researchers found the answer in the anterior cingulate cortex (ACC), a region in the prefrontal lobe of the brain that is associated, among other things, with the recognition and evaluation of social processes and the development of emotional awareness. The mouse model showed that in females who have not been pregnant or given birth, the ACC gets activated when they acquire maternal behaviour upon first contact with pups. "Our observations have demonstrated that, through repeated experience with pups, the virgin females are capable of learning maternal behaviour that fully resembles those of mothers after delivery," explains project leader Daniela Pollak, reporting from her research. The study revealed that during this learning process ACC activity is controlled by an excitatory feedback circuit involving a specific group of neurons in a central brain region (the thalamus). Learning through repeated experience Maternal behaviour is defined, among other things, by sensitivity and responsiveness to signals of infant needs. It is instinctively displayed in virtually all mammals and upon first contact with newborns immediately after delivery. In some species, such as rodents, even animals that have never given birth may exhibit maternal care behaviour toward newborns. In this case, the care behaviour, such as returning displaced pups from outside the nest back into the nest area, where they are warm and protected from predators, are acquired through repeated experience with the pups. We know, for example from observations in adoptive parents, that humans can also learn parental behaviours. Various pathological conditions, such as postpartum depression or postpartum psychosis can lead to alterations in maternal behaviour and disrupt the mother-child bonding process. "By showing that maternal behaviours can be acquired and identifying the underlying neuronal circuits in the brain that control this acquisition, we are creating a potential basis for developing therapeutic options for these clinical situations," says Daniela Pollak, outlining the translational relevance of the study results, which were obtained in collaboration with Tibor Harkany from the Division of Molecular Neurosciences at MedUni Vienna's Center for Brain Research.

Courtesy of JHVEPhoto/GettyImages On Thursday, Pfizer announced the U.S. Food and Drug Administration granted its combinatorial therapeutic ervogastat/clesacostat Fast Track Designation. The therapeutics are intended for the treatment of Non-Alcoholic Steatohepatitis (NASH) with liver fibrosis. NASH is a type of non-alcoholic fatty liver disease marked by inflammation and damage of the liver in addition to a buildup of fat. The inflammation and damage to the liver can cause fibrosis and cirrhosis, leaving the organ scarred and permanently damaged while also increasing the risk for liver cancer. The cause of NASH is still up for debate, although researchers believe obesity, Type II Diabetes and genetics may play a role. Treatment for NASH is desperately needed, as the FDA has approved no treatments for the condition, which affects an estimated 17 million people in the U.S. Pfizer is now entering the race, armed with ervogastat and clesacostat. In nonclinical studies and a Phase IIa clinical study of the combination therapy, the treatment was effective in reducing liver fat while demonstrating a favorable safety and tolerability profile. Now, the treatment is being studied in an ongoing Phase II clinical trial evaluating the impact of the treatment on the resolution of NASH or improvement in liver fibrosis. The study is anticipated to be completed in 2024 and will inform a future Phase III clinical trial, including an arm that will investigate ervogastat as a monotherapy. "Receiving Fast Track designation from the FDA reinforces Pfizer's belief in ervogastat/clesacostat as a potential treatment for NASH, a serious, progressive liver disease with no currently approved therapies," said Pfizer senior vice president and chief development officer of interal medicine James Rusnak, M.D., Ph.D., in a press release. "We are proud to be advancing this investigational combination as part of our goal to develop innovative medicines to address some of the world's most widespread health challenges that affect millions of people—including diseases like NASH." The treatment targets two key enzymes that regulate lipid or fat metabolism called diacylglycerol O-acyltransferase 2 (DGAT2) and acetyl-CoA carboxylase (ACC). Prior research has shown that inhibiting DGAT2 and ACC can lower liver fat in patients with non-alcoholic fatty liver disease, and Pfizer believes the combination therapy will improve inflammation and fibrosis. A recent report by Vision Research Reports states that the NASH clinical trials market size is predicted to hit $4.1 billion by 2030, likely due to rising healthcare expenditure, cases of obesity and the prevalence of NASH in the population. Clinical trials for NASH have also likely grown due to newer and better imaging modalities, which can be used in early-phase NASH trials to assess liver fat content and fibrosis stage. There are currently 22 listed studies recruiting for patients with NASH. Earlier this month, Lipocine announced positive results from its Open-Label Extension study of LPCN 1144, which is an orally delivered prodrug of testosterone. Results showed that the treatment was well-tolerated, and liver injury markers reduced significantly and were maintained with extended treatment.