DIADEM NAMES CLINICAL DIAGNOSTICS INDUSTRY VETERAN PAUL KINNON AS CEO

—Kinnon Joins to Lead Development and Commercialization of First Minimally Invasive Blood-Based Prognostic Test for Early Alzheimer’s Disease—

—Accessible Early Diagnosis Will Transform Treatment by Enabling Development of Effective Therapeutic Interventions to Slow or Stop Disease Progression—

Milan, ITALY – October 19, 2020 – Diadem srl, a company developing the first blood-based test for the prediction of early onset Alzheimer’s disease, today announced that Paul Kinnon has been named Chief Executive Officer. Mr. Kinnon brings Diadem extensive global executive experience in successfully developing and commercializing innovative diagnostic and life science technologies in Europe and the U.S.

“Alzheimer’s disease and other dementias are among the greatest public health crises of our time, afflicting more than 50 million people worldwide,” noted Mr. Kinnon. “Development of effective therapies has been hindered by the difficulty of prediction and diagnosis, which makes early, effective intervention impossible.”

Kinnon continued, “Diadem’s transformational technology for the first time makes it possible to diagnose Alzheimer’s early in the disease process and to predict whether the disease will progress. This will allow patients to seek treatment at a time when it is still possible to impact disease progression and preserve function. Our AlzoSure® test is blood-based, non-invasive and potentially widely accessible. I am honored to have the opportunity to work with the talented Diadem team to advance the development and commercialization of this breakthrough technology that could improve the lives of millions.”

Kinnon served as chief executive officer at PredictImmune, publicly traded Transgenomic, and ZyGEM Corp. He held senior executive positions at Life Technologies (now ThermoFisher), Guava Technologies and Cellomics, raising substantial funding, creating global partnerships and increasing shareholder returns. Kinnon has a proven strategic and commercialisation track record of developing and bringing novel technologies and products to global markets rapidly and efficiently. He serves on the boards of both public and private companies and has significant expertise in corporate governance, corporate restructuring, and M&A and divestitures.

“We are delighted to have an experienced and successful global industry veteran like Paul at the helm of our exciting company as it prepares to move into the commercial phase of growth,” said Gerald Möller, Chairman of the Board of Diadem and former CEO of Boehringer Mannheim. “Diadem’s minimally invasive technology for the early diagnosis of Alzheimer’s disease has enormous potential to transform the treatment of dementia and help spur the availability of effective new therapies. We look forward to working with Paul to advance the clinical development and commercialization of this important technology.”

Diadem is developing AlzoSure®—a plasma-based biomarker test that has been validated in early studies to accurately predict the probability a patient with mild cognitive impairment will progress to Alzheimer’s disease. The company’s patented technology measures conformational changes in the p-53 pathway. It targets Unfolded p-53, which is over-expressed in Alzheimer’s patients, using an analytical method that includes a proprietary antibody and target sequences developed by Diadem. Further clinical studies are underway, and the company plans a global launch in collaboration with strategic partners in 2021.

DEVELOPMENT OF BLOOD-BASED ALZHEIMER’S PROGNOSTIC PROPELS DIADEM TO FINALIST STATUS FOR BOTH THE GAETANO MARZOTTO COMPANY PRIZE AND 2030 SOCIAL IMPACT SPECIAL PRIZE

—Prestigious Awards Celebrate Entrepreneurial Company Innovation and Pioneering New Products Supporting UN Sustainable Development Goals —

—Diadem’s Minimally Invasive Blood-Based AlzoSure® Prognostic Test for Early Alzheimer’s Disease Selected for Potential to Help Transform Management of this Devastating Global Disorder—

—Diadem Also Provides Update on Intellectual Property Status of the AlzoSure Technology—

Milan, ITALY – November 16, 2020 – pool of 600 applicants. The companies were analyzed by experts representing relevant public, private, financial, technological and specialist sectors. Diadem was one of five finalist companies for the Gaetano Marzotto Company Prize and one of six finalists for the Gaetano Marzotto 2030 Social Impact Special Prize.

“We are incredibly honored to be selected as a finalist for both the Gaetano Marzotto Company Prize and the inaugural Gaetano Marzotto 2030 Social Impact Special Prize, which highlights young companies whose products have the potential to advance the UN Sustainable Development Goals and reduce inequality,” said Paul Kinnon, CEO of Diadem. “Alzheimer’s disease and other dementias afflict more than 50 million people worldwide. Our revolutionary AlzoSure prognostic test could transform Alzheimer’s disease management, enabling effective interventions much earlier in the disease process. Importantly, as a blood-based, non-invasive biomarker assay, we expect AlzoSure to be widely available to older populations around the globe, combining great clinical and commercial potential with exceptional accessibility.”

Diadem also provided an update on its intellectual property. Diadem has taken steps to patent the innovative AlzoSure technology, including its proprietary antibody and the actual process for the assay. Patents have been filed in Italy, the US and other regions including China and Japan. US Patent 10,183,990 B2, which issued last year, covers Diadem’s antibody, immunodiagnostic kit and associated in vitro methods of diagnosing Alzheimer’s disease and/or the predisposition to develop Alzheimer’s disease. It covers the company’s game-changing plasma-based technology that measures conformational changes in the p-53 pathway, targeting Unfolded p-53, which is over-expressed in Alzheimer’s patients, and applies an analytical method that includes a proprietary antibody and target sequences developed by Diadem. A similar patent, EP 3 201 234 B1, issued in the European Union in 2018.

Mr. Kinnon commented, “Diadem plans to continue to aggressively protect our technology and products by filing further patents globally and prosecuting those currently in process. We believe our AlzoSure technology can help transform the prediction and treatment of early Alzheimer’s disease, and we are committed to protecting the innovative intellectual property that makes the test possible.”

Diadem’s AlzoSure is a plasma-based biomarker test that has been validated in early studies to accurately predict the probability a patient with mild cognitive impairment will progress to Alzheimer’s disease. Further clinical studies are underway, and the company plans a global launch in collaboration with strategic partners in 2021.

For more information on the Gaetano Marzotto Prizes, visit www.premiogaetanomarzotto.it/en/homepage/

DIADEM NAMES DR. TAMAS BARTFAI CHAIR OF ITS MEDICAL ADVISORY BOARD

—Dr. Bartfai Brings Broad Academic and Pharma Industry Experience to Medical Advisory Board Comprised of Distinguished Alzheimer’s Disease Researchers and Opinion Leaders —

Milan, ITALY – December 1, 2020 – Diadem srl, a company developing the first blood-based test for the early prediction of Alzheimer’s disease (AD), today announced that noted neuroscientist and Alzheimer’s disease researcher Tamas Bartfai, PhD, has been named Chair of its Medical Advisory Board (MAB). Dr. Bartfai brings a unique combination of broad industry and academic research experience to Diadem. The Diadem MAB includes other well-known international AD experts representing a variety of disciplines, including Jeffrey Cummings, MD, ScD, Joy Chambers-Grundy Professor of Brain Science and Director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Las Vegas; Robert Dean, MD, PhD, formerly Senior Medical Fellow and Director of the Department of Diagnostics & Experimental Medicine at Eli Lilly & Co.; Anne Fagan, PhD, Professor of Neurology and Biomarker Core Leader at Washington University School of Medicine in St. Louis; and Giovanni Frisoni, MD, PhD, Professor of Clinical Neuroscience and Head of the Memory Clinic at the Faculty of Medicine of the University of Geneva, Switzerland.

“We are fortunate to have an MAB comprised of distinguished world-class neuroscientists and are delighted that Professor Bartfai is coming onboard as Chair,” said Paul Kinnon, CEO of Diadem. “Tamas brings us his exceptionally broad experience in the discovery and development of important new therapies for neurological disorders, including Alzheimer’s disease. His work spans major academic research organizations, global pharmaceutical leaders and biotech enterprises. The breadth of his experience and his deep knowledge of existing and cutting-edge neurological research should be invaluable as we advance Diadem’s innovative blood-based prognostic test for AD.”

Dr. Bartfai is an international expert in the development of drugs targeting neurological diseases, including Alzheimer’s disease. Formerly, Dr. Bartfai was a Professor and Chairman of Molecular and Integrative Neurosciences and Director of the Dorris Neuroscience Center at the Scripps Research Institute, as well as an Adjunct Professor at Stockholm University, the University of Oxford and the University of Pennsylvania. Over the past decades, Dr. Bartfai has served as a drug development senior executive or consultant to numerous pharmaceutical companies, including Astra Zeneca, Roche, Novartis and Pfizer. He has been a consultant to biotech venture capitalists and also helped launch a number of biotech start-ups. Dr. Bartfai participated in the development of about a dozen approved drugs for neurological diseases and other conditions. He is the author or co-author of more than 400 peer-reviewed publications and several books and is the recipient of awards for his pioneering work on neuropeptides and other topics. Dr. Bartfai earned a BSc degree from Eötvös Loránd University in Budapest and a PhD from Stockholm University.

Dr. Bartfai commented, “Improved treatments for AD will require broad access to better ways of predicting and diagnosing the disorder, since we know the pathology begins years before symptoms appear. I am optimistic about the potential of Diadem’s blood-based biomarker approach to help make early AD prognosis feasible and widely accessible, which is critical in view of the global scale and large numbers of people at risk for this devastating disorder. I look forward to working with the talented Diadem scientific team and distinguished MAB members to help advance this program that has game-changing potential.”

The other MAB members include:

Jeffrey Cummings, MD, ScD, a world-renowned Alzheimer’s researcher and clinical trials leader. He is the Joy Chambers-Grundy Professor of Brain Science and Director of the Chambers-Grundy Center for Transformative Neuroscience at the University of Las Vegas. Previously he was Founding Director of the Cleveland Clinic Lou Ruvo Center for Brain Health. Dr. Cummings was also Director of the Mary S. Easton Center for Alzheimer’s Disease Research and Director of the Deane F. Johnson Center for Neurotherapeutics, both at the University of California, Los Angeles.

Robert Dean, MD, PhD, who served as a Senior Medical Fellow and Clinical Research Pathologist at Eli Lilly & Company for more than 20 years, focusing on biomarker discovery with application to translational research for diagnostics and pharmaceutical development. As Director of the Department of Diagnostics & Experimental Medicine at Lilly, Dr. Dean worked in support of numerous diagnostics development programs, including those for neurodegenerative disease.

Anne Fagan, PhD, is a Professor of Neurology at Washington University School of Medicine in St. Louis. She is an expert in the development of biomarkers for Alzheimer’s disease, especially before symptoms appear. Dr. Fagan leads the biomarker core for large multi-site studies and biobanks and was instrumental in developing the biomarkers program at the Knight Alzheimer’s Disease Research Center (ADRC). She is an ADRC investigator and serves as the Biomarker Core Leader for several large national and international research programs. For years she and her lab have also been involved in global biomarker standardization efforts for neurological diseases, with the goal of bringing validated biomarkers to clinical practice.

Giovanni Frisoni, MD, PhD, is a world leading imaging expert and Professor of Clinical Neuroscience and Head of the Memory Clinic at the Faculty of Medicine of the University of Geneva. He is a researcher at the university’s Neurocenter, which focuses on clinical and translational research in Alzheimer’s disease, especially the use of neuroimaging and other biomarkers in persons with or at risk for cognitive impairment. Dr. Frisoni has served as the principal or co-principal investigator or scientific coordinator for important research studies that have progressed clinical neuroimaging and the understanding of AD and other cognitive disorders, and he has published widely on these topics.

DIADEM PRESENTS CLINICAL DATA AND COMMERCIALIZATION PLANS FOR ITS ALZOSURE® PROGNOSTIC BIOMARKER TEST AT 2020 ALZHEIMER’S DISEASE INTERNATIONAL CONFERENCE

—Blood-Based AlzoSure Assay Has Potential to Transform Management of Alzheimer’s Disease by Identifying Patients Early in the Disease Process—

Milan, ITALY – December 11, 2020 – Diadem srl, a company developing the first blood-based test for the early prediction of Alzheimer’s disease (AD), today reported that it hosted a Symposium on its prognostic biomarker test at the 34th Annual Conference of Alzheimer’s Disease International (ADI). Diadem presented early clinical data for its AlzoSure® Predict assay in the Symposium, outlined initial commercialization plans and hosted an expert panel. To view a replay of the Symposium, click here.

AlzoSure® Predict is a simple, non-invasive plasma-based biomarker test that has been validated in early studies to accurately predict the probability a patient with asymptomatic, mild cognitive impairment (MCI) will progress to dementia due to AD The company’s patented technology measures a conformational variant of p-53 (U-p53), which is over-expressed in Alzheimer’s patients, using an analytical method that includes a proprietary antibody and target sequences developed by Diadem. Further clinical studies are currently underway, and the company plans a global launch in collaboration with strategic partners in 2021.

Diadem CEO Paul Kinnon and Simona Piccirella, PhD, Vice President of Product Development & Operations, presented an overview of promising initial clinical data showing the potential utility of AlzoSure Predict for identifying which patients will progress from asymptomatic MCI to AD. They also discussed the company’s clinical, regulatory and commercialization plans.

Symposium panelists included Diadem Medical Advisory Board AD experts Dr. Tamas Bartfai, Dr. Jeffrey Cummings and Dr. Anne Fagan. In an interactive session, they discussed the scientific background of the AlzoSure Predict biomarker test, its performance to date, and initial clinical validation data. They also explored how AlzoSure tests could fit into and impact the patient clinical pathway, along with their suitability and potential to improve patient treatment and long-term outcomes.

As part of the Symposium, Diadem presented early clinical validation data comparing AlzoSure Predict’s prognostic performance with historical diagnostic results. AlzoSure accurately “predicted” cognitive decline to Alzheimer’s dementia, achieving Positive and Negative Predictive Values (AUC’s) of greater than 90%, regardless of cognitive status (cognitively normal or MCI) at the time of the test. AlzoSure showed superior ability to predict cognitive decline to Alzheimer’s dementia compared to “gold standard” PiB-PET imaging, and AlzoSure predicted progression to Alzheimer’s dementia significantly better than amyloid and tau-based assays combined, using the same baseline characteristics.

Citing AD’s high incidence and global nature, panelist Dr. Anne Fagan noted the importance of availability and scalability when testing for Alzheimer’s disease. “The beauty of the biomarker test is that it is available. It is a simple blood test and people are used to that. It can be administered in the physician’s office and serve as the basis for discussions with family members and caregivers. I think it’s a very attractive option.”

Panelist Dr. Jeff Cummings commented, “We are in the age of biomarkers right now that will hopefully lead us to the age of therapies.” He noted the prognostic importance of Diadem’s p53 biomarker that “can tell us which patients are declining,” thereby enabling AD drug developers to select the right patients to include in their clinical trials. “This is the kind of biomarker test companies are looking for,” Dr. Cummings concluded.

Further validation studies of AlzoSure Predict involving about 1,000 individuals are expected to be completed during the first half of 2021.

“We were pleased at the opportunity to share the encouraging early clinical data and our commercialization plans for our AlzoSure Predict prognostic assay,” said CEO Kinnon. “Based on these results, we believe that our ongoing studies will confirm its ability to forecast which patients will go on to develop symptomatic AD up to six years before symptoms appear, well before any current diagnostic is accurate. We see AlzoSure as a

game-changer in Alzheimer’s disease–enabling earlier treatment for patients and the development of more effective AD therapies for administration before brain damage and loss of cognitive function are irreversible.”

The virtual Diadem Symposium, AlzoSure–A Simple Blood Test that Predicts Clinical Dementia/Alzheimer’s Before Cognitive Impairment: Implications for the Diagnostic Pathway and Treatment with Disease-Modifying Agents—took place from 9:05-10:05am GMT on December 11, 2020. To view a replay of the Symposium, click here.

NEW SCIENTIFIC PUBLICATIONS SHOW DIADEM’S BLOOD-BASED ALZOSURE® BIOMARKER TEST CAN PREDICT WHICH PATIENTS WILL PROGRESS TO ALZHEIMER’S DISEASE YEARS BEFORE SYMPTOMS OCCUR

—Published Studies Explore How a Variant of p53 Contributes to the Development of Alzheimer’s Disease (AD) and How Plasma Levels of this Variant Can Serve as a Prognostic Biomarker Predicting Progression to AD Early in the Disease Process—

Milan, ITALY – February 01, 2021 – Diadem srl, a company developing the first blood-based test for the early prediction of Alzheimer’s disease (AD), today announced the publication of three new scientific studies that support the utility of its biomarker assay to identify individuals at high risk for AD. The publications describe the role of a conformational variant of the p53 protein ( U-p53AZ) in the pathogenesis of AD, as well as its applicability as a predictive biomarker to identify individuals likely to progress to AD up to six years before symptoms appear. Two of the papers report the results of early studies that confirm the accuracy of the U-p53AZ-based assay, in development by Diadem as AlzoSure® Predict, as a prognostic test for AD.

Diadem is developing the AlzoSure assay as a simple, non-invasive plasma-based biomarker test to accurately predict the probability that a patient with asymptomatic mild cognitive impairment (MCI) will progress to Alzheimer’s dementia. The company’s patented technology uses an analytical method that includes a proprietary antibody designed to bind to U-p53AZ and target sequences developed by Diadem. Further clinical studies of the assay are underway, and the company plans a global launch in collaboration with strategic partners later this year.

“Together, these studies highlight why we are so excited about the potential of AlzoSure to have a major impact on this devastating disease,” said Paul Kinnon, CEO of Diadem. “They describe how this conformational variant of p53 contributes to the ongoing pathology of AD, as well as how its role in disease progression makes it useful as a biomarker to identify patients whose neurons are already under attack. The simplicity and affordability of our blood-based biomarker test mean that it will be available to individuals in primary care settings, which will make widespread screening feasible. This is turn will help spur the development of new drugs for AD, which now will be able to be widely administered early in the disease process, when the chances for slowing and stopping the cognitive ravages of AD are the greatest.”

The first publication1, The pleiotropic role of p53 in functional/dysfunctional neurons: focus on pathogenesis and diagnosis of Alzheimer’s disease, was published in Alzheimer’s Research & Therapy. It reviews the role of the p53 protein in the development of Alzheimer’s disease. As “the guardian of the genome”, p53 is most associated with tumor suppression. However, growing evidence shows that dysregulated p53 activity may also contribute to changes in the brain and peripheral nervous system during the early stages of AD. The review describes how p53 dysregulation may exacerbate AD pathology by interfering with a variety of key defense mechanisms that protect neurons and prevent their degeneration. These mechanisms include regulation of inflammation, control of synaptic function, maintenance of redox homeostasis, reduction of amyloid β peptides and inhibition of neuronal cell cycle re-entry. The authors describe the possible causes of this p53 conformational change and its impact on neuronal function. The conformational variant of p53 has been found in peripheral neuronal cells in patients with mild cognitive impairment (MCI) and with AD. As has been previously described in the scientific literature, levels of unfolded p53 are significantly higher in peripheral cells derived from patients with AD compared with non-demented controls and are also significantly higher than in patients with Parkinson’s disease and other types of dementia. Researchers also expect that unfolded p53 is present in the brain of dementia patients, but this has yet to be confirmed. Because unfolded p53 appears early in the disease process and helps fuel the increasing pathology seen over time in AD, the authors conclude that it has potential to serve as a biomarker for the early detection of AD.

The second article2, A conformation variant of p53 combined with machine learning identifies Alzheimer disease in preclinical and prodromal stages, was recently published in the Journal of Personalized Medicine. It reports on a study from the University of Brescia assessing Diadem’s blood-based prognostic test for AD. The assay measures the conformational variant of p53 (U-p53AZ) as a biomarker to identify individuals at high risk for the early onset of the condition, using a patented monoclonal antibody specifically developed for this purpose by Diadem researchers.

In their introduction, the researchers point out that while U-p53AZ (referred to in this study as U-p53 2D3A8+) is a relatively unknown player in AD, it has demonstrated the features needed for a credible biomarker of biological processes involved in the development of AD. In their prior work, they had identified the increased expression of unfolded p53 in fibroblast and blood cells derived from both AD patients and MCI patients who converted to AD, as well as in AD and MCI plasma specimens. The fact that U-p53AZ is highly expressed in both the preclinical and early symptomatic stages of AD make it a good candidate as a prognostic biomarker.

In this study, the researchers confirmed that the Diadem-developed and patented antibody is a reliable tool for recognizing the U-p53AZ conformational variant. The approach was tested in a longitudinal study of 375 subjects in well-characterized cohorts. U-p53AZ plasma levels correlated with the clinical evolution of the disease, as described by longitudinal analysis, and showed high accuracy in discriminating individuals who converted to AD versus non-converters. The assay achieved an overall 86.7% agreement with clinical diagnosis. Importantly, the algorithms used in the assay also accurately classified MCI patients who will develop AD (AUC = 0.92) . These subjects were stratified using recognized AD markers from cerebral spinal fluid. A machine learning approach to predict AD risk was also developed that combined measurements of U-p53AZ plasma levels with a standardized test for cognitive impairment and levels of apolipoprotein E-4 (a protein subtype that is implicated in AD).

The researchers note that the Alzheimer’s Precision Medicine Initiative (APMI) working group recommends that a blood-based AD biomarker should provide a tool in the primary care setting to assess subjects who are subjectively cognitively normal or have very early signs of cognitive decline, allowing identification of the at-risk subset who require further evaluation and early intervention. The study authors conclude that the biomarker test based on measurements of plasma levels of U-p53AZ represents a promising blood-based biomarker for AD that could meet the urgent need identified by the APMI.

The third publication, Discovery of simple blood based test to predict early onset of Alzheimer’s using standard clinical mass spectrometry platforms, has just been released as a preprint and is also being submitted to a peer-reviewed journal for publication. It reports on another early longitudinal study of Diadem’s AlzoSure prognostic assay. The authors begin by noting that despite the increasing number of individuals affected by AD every year, no effective therapy has yet been approved. A major factor underlying the lack of disease-modifying therapeutics is the inadequacies of current diagnostic methods, which only identify AD years after molecular damage to the central nervous system has been underway. Earlier diagnosis would make it feasible to initiate disease-modifying therapies much earlier in the disease process.

Knowing that the p53 conformational variant (U-p53AZ) had been correlated with AD, the researchers developed a mass spectrometry method for precise quantification of the p53 conformational variant from plasma. They analysed 107 plasma samples from patients with known clinical outcomes at different time points and tested the prognostic performance of the AD-specific U-p53AZ peptide (AZ 284) in different sets of individuals, progressing from cognitive normal or mild cognitive impairment to AD dementia. Brain amyloid burden by PET imaging data was available for most of the plasma samples and apolipoprotein E-4 levels were also measured. Participants were classified as cognitively unimpaired (CU), as MCI, or as presenting symptomatic AD. For each diagnostic group, changes of status at the follow-up visits (after 18 and 36 months) were reported.

Using this well-characterized longitudinal cohort, the researchers demonstrated that U-p53AZ successfully predicted MCI progression to AD at least 36 months earlier, and in a cognitively unimpaired subject, it did so at least six years before symptoms became apparent. Diagnostic performance of the U-p53AZ peptide in the individuals progressing from cognitive normal and mild cognitive impairment to AD dementia confirmed that quantitative analysis of U-p53AZ is a reliable tool for prediction of AD progression up six years in advance of diagnosis, with AUC≥ 90%. The authors conclude that taken together, the results support the implementation of the U-p53AZ biomarker as an affordable and powerful prognostic tool for the early, non-invasive diagnosis of AD in individuals with no symptoms or with early symptoms of cognitive impairment. The study authors also note that availability of this type of accurate, non-invasive, inexpensive test could enable clinical trials for new AD therapies much earlier in the course of the disease when interventions are more likely to be effective. They also point out that it would be helpful to confirm these findings in a larger study. Diadem is currently conducting further validation studies in about 1000 subjects.

DIADEM PRESENTS NEW DATA AT AAIC® SYMPOSIUM SHOWING ITS BLOOD-BASED BIOMARKER TEST ACCURATELY PREDICTS PROGRESSION TO ALZHEIMER’S DISEASE 7 YEARS BEFORE SYMPTOMS OCCUR

—Analysis of 224 Longitudinal Patient Samples Confirms Diadem’s Prognostic Biomarker Can Predict Progression to AD Early in the Disease Process with >90% Accuracy—

—Study Results Also Available in Newly-Released Preprint—

Milan, ITALY – May 13, 2021 – Diadem srl, a company developing the first blood-based test for the early prediction of Alzheimer’s disease (AD), today announced new data showing that its AlzoSure® prognostic biomarker test can accurately predict progression to Alzheimer’s disease six to seven years before symptoms appear. The new study results are being presented today at the 2021 Alzheimer’s Association International Conference® (AAIC) Satellite Symposium. Results of the study are available as a preprint1 and are also being submitted for publication in a peer-reviewed journal.

The Diadem assay uses a proprietary antibody to measure blood levels of a conformational variant of the p53 protein that has been implicated in the pathogenesis of AD. Previous studies suggest that this p53 variant has utility as a predictive biomarker to identify individuals likely to progress to AD up to six years before symptoms appear.

The new study is based on health data collected from 224 participants in the Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Aging (AIBL). The well-characterized cohort includes extensive longitudinal patient data and plasma samples. The prognostic performance of Diadem’s biomarker test in predicting progression to Alzheimer’s dementia was high, with “area under the curve” values (a measure of the accuracy of a quantitative diagnostic test) above 0.90 for both preclinical pre-symptomatic patients and for prodromal stage patients beginning to manifest early dementia symptoms.

The study results indicated promising positive and negative predictive values of about 90% when predicting the progression to AD dementia more than 6 years prior to symptom onset. Additionally, the prognostic performance of the Diadem biomarker test was superior to covariate measures including age, gender, and APOE-related genetic susceptibility, either alone or in combination with amyloid status. The Diadem biomarker test also achieved high diagnostic performance in the ability to differentiate cognitively normal individuals from patients with AD dementia.

The data are being presented today at the AAIC Satellite Symposium by Simona Piccirella, PhD, Diadem’s Vice President of Product Development and Operations. Dr. Piccirella noted, “Our ability to accurately identify individuals at high risk of progressing to AD early in the disease process, when effective disease-modifying interventions are still feasible, is a game-changer. Our simple, affordable and accessible blood-based technology will enable individuals to be widely screened in primary care settings, setting the stage for achieving tangible progress against this devastating disease that could benefit millions of people worldwide.”

Diadem is developing the AlzoSure assay as a simple, non-invasive plasma-based biomarker test to accurately predict the probability that a patient with asymptomatic mild cognitive impairment (MCI) will progress to Alzheimer’s dementia. The company’s patented technology uses an analytical method that includes a proprietary antibody designed to bind to the conformational variant U-p53AZ protein and target sequences developed by Diadem. Diadem is currently conducting further validation studies in about 1000 subjects, with additional results expected this year. The company plans to initiate a global launch in collaboration with strategic partners within the next 12 months.

DIADEM ANNOUNCES PUBLICATION OF CLINICAL DATA SHOWING ITS ALZOSURE® BIOMARKER TEST ACCURATELY PREDICTS PROGRESSION TO ALZHEIMER’S DISEASE SIX YEARS BEFORE DIAGNOSIS

—Longitudinal Data from 482 Patients Validates that AlzoSure® Can Predict Progression to AD Early in the Disease Process with >90% Accuracy—

—AlzoSure Predict Identifies Patients Who Will Progress to Alzheimer’s Up to Six Years in Advance of Other Diagnostic Tests with Simple Blood Draw—

—AlzoSure Predict Demonstrates Superior Performance in Predicting Progression to AD than PET Imaging or CSF Biomarkers—

—Clinical Validation Interim Data Are Being Presented at 21st BioEquity Europe Conference May 18-19, 2021—

Milan, ITALY – May 18, 2021 – – Diadem srl, a company developing the first blood-based test for the early prediction of Alzheimer’s disease (AD), today announced top-line interim results from a global clinical validation study of its AlzoSure® Predict prognostic biomarker test, which can accurately predict progression to Alzheimer’s disease years before symptoms appear. The interim data are being presented today at the 2021 BioEquity Europe virtual conference. Overall, they confirm the results of a Discovery Cohort analysis presented at the AAIC Satellite Symposium earlier this month. The new data show that AlzoSure Predict identifies those Cognitive Normal and Minor Cognitive Impairment (MCI) patients who will progress to ADdementia with high accuracy (>90% PPV) and confirm its capability to discriminate different stages of cognitive decline from asymptomatic to mild impairment to full dementia. In this cohort, AlzoSure Predict had very good selectivity for distinguishing between patients progressing to AD dementia and Other Dementia (OD), and It also demonstrated superior predictive performance to PET imaging and cerebral spinal fluid (CSF) biomarkers across all groups.

The Diadem AlzoSure Predict assay uses a proprietary antibody to measure blood levels of a conformational variant of the p53 protein that has been implicated in the pathogenesis of AD. Previous studies suggest that this p53 variant has utility as a predictive biomarker to identify individuals likely to progress to AD up to six or seven years before symptoms appear.

The interim Clinical Validation analysis is based on longitudinal data from 482 patients from major biobanks in Australia, Europe and the US—the first cohort of the more than 1000 patients globally who will ultimately be included. They include individuals over the age of 50 at different stages of cognitive decline: Cognitive Normal, MCI and Demented (either AD or OD). Patients were followed longitudinally for up to 144 months. The data include comparative results from PET imaging, cognitive test performance and CSF biomarker and other blood biomarker assays. Complete data from the Clinical Validation analysis are being submitted for publication in a peer-reviewed journal.

The data are being presented today at BioEquity Europe by Diadem’s CEO Paul Kinnon. Mr. Kinnon noted, “Last week at the AAIC Satellite Symposium we presented exciting data from our Discovery cohort study showing that our AlzoSure Predict prognostic biomarker test accurately identifies individuals who will progress to Alzheimer’s dementia six or seven years before symptoms appear or are detectable using traditional diagnostic methods.”

Mr. Kinnon continued, “These interim data from our larger Clinical Validation study confirm and extend those results. This is good news for the millions of families worldwide who will confront AD in the coming years, since our simple, accessible blood-based assay will allow for therapeutic interventions early in the disease process, when slowing or stopping disease progression is far more feasible. It will also enable more effective clinical trials of investigative therapies for AD. We look forward to sharing the full results from the Clinical Validation study in the coming months.”

Diadem is developing the AlzoSure assay as a simple, non-invasive plasma-based biomarker test to accurately predict the probability that a patient with asymptomatic mild cognitive impairment will progress to Alzheimer’s dementia. The company’s patented technology uses an analytical method that includes a proprietary antibody developed by Diadem designed to bind to the conformational variant U-p53AZ protein and its target sequences. Diadem is currently conducting further validation studies in about 1000 subjects, with additional results expected this year. The company plans to initiate a global launch in collaboration with strategic partners within the next 12 months.

About Alzheimer’s Disease
There are about 50 million people suffering from dementia worldwide. Alzheimer’s disease is the most common form and accounts for 60-70% of cases. At present there are no disease modifying treatments for Alzheimer’s, and therapies to treat symptoms are limited. There are about 10 million new cases per year, and the incidence is rising rapidly as the population ages. The current total cost of care is enormous–estimated at $1 trillion in the U.S. annually and expected to double by 2030. Currently, diagnosis of Alzheimer’s disease is slow, inconclusive, invasive and expensive. Development of effective therapies for Alzheimer’s has been hindered by the lack of accurate and cost-effective prognostic and diagnostic methods.

About Diadem
Diadem was founded as a spin-off of the University of Brescia (Italy). The company is developing the first blood-based prognostic test for the early detection of dementia, with a focus on Alzheimer’s disease. The lack of accurate, accessible and affordable diagnostic tools is a major contributor to the absence of effective treatments for this devastating condition. As a result, patients are not diagnosed until late in the illness, when effective treatment is no longer possible. Diadem’s rapid, accurate and cost effective blood-based prognostic test makes it possible for the first time to identify patients early in the disease process, when effective interventions and better outcomes are far more feasible. The utility of the approach has been demonstrated in early clinical studies. Additional retrospective and prospective clinical trials are ongoing and planned to further validate clinical claims and support widespread adoption and use. Diadem’s founding lead investor is Milan-based Panakes Partners, a venture capital firm that finances promising high potential biomedical companies in Europe and Israel. Diadem is preparing for rapid commercialization of its initial Alzheimer’s prognostic via a global launch in collaboration with strategic partners.