Diadem Unveils Novel Findings on Early Alzheimer’s Disease Detection Using p53-Specific Antibody at CTAD 2024

Milano, Italy, November 1, 2024 – Diadem SpA, in partnership with researchers from the University of Texas Medical Branch, led by Prof. Rakez Kayed from the Mitchell Center for Neurodegenerative Disorders, presented groundbreaking findings at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference. The study focused on U-p53AZ, a conformational variant of the p53 protein linked to Alzheimer’s disease (AD). Using a U-p53AZ-specific antibody developed by Diadem, the team identified the presence of this misfolded protein in human brain tissue, providing critical insights into AD pathology.

Managing cognitive decline and dementia is particularly challenging in the early stages, partly due to the lack of reliable and affordable biomarkers. Misfolding of the p53 protein, detected by U-p53AZ, has been developed as a prognostic tool for AD. Previous studies showed that measuring U-p53AZ levels in plasma using a proprietary antibody could predict the risk of significant cognitive deterioration in Alzheimer’s disease (AD). This current study extends those findings by applying the U-p53AZ antibody to brain tissue, further validating its role in AD diagnosis.

Researchers applied U-p53AZ to brain samples from various Braak stages, which track AD progression. The antibody selectively bound to misfolded p53 in AD tissues, with minimal binding in healthy controls. Co-staining with phosphorylated tau (pTau), a key AD marker, reinforced the association between p53 misfolding and tau pathology, suggesting a strong link to AD progression.

Prof. Rakez Kayed stated, “The co-localization of misfolded p53 with phosphorylated tau suggests a mechanistic interaction that warrants further investigation, particularly as a target for early diagnostic intervention.” His comments underscore the significance of the findings in identifying new diagnostic and therapeutic strategies.

Dr. Sam Agus, Chief Medical Officer at Diadem, added, “Our results demonstrate that U-p53AZ not only identifies a conformation-specific form of p53 linked to Alzheimer’s disease but also correlates with disease severity through Braak staging.

The study expands on prior work (Piccirella et al, JPAD, 2022), positioning U-p53AZ as a robust tool for both early and advanced AD detection. Its potential for clinical application in diagnostic settings is significant, particularly in light of its ability to distinguish AD-related p53 misfolding from normal p53 conformations.

For more information, contact:
Diadem:
Michael Rasche
CEO
execadmin@diademdx.co.uk

About Diadem SpA
Diadem SpA is a leader in diagnostic solutions for Alzheimer’s and neurodegenerative diseases. Based in Milano, Italy, Diadem focuses on early detection to improve patient outcomes.

Diadem Appoints Michael Rasche as Chief Executive Officer

Brings International Perspective and Extensive Experience Across Multiple Life Sciences Sectors to Advance Diadem’s Pioneering Prognostic Technology for the Early Detection of Alzheimer’s Disease

Milan, Italy – July 10, 2024 – Diadem SpA, (Diadem), a company developing one of the first blood-based tests for the early and accurate prediction of clinical progression to Alzheimer’s disease (AD), today announced that Michael Rasche has been named Chief Executive Officer (CEO) and a member of the Board of Directors. Mr. Rasche brings Diadem more than three decades of experience in driving life sciences  innovations to commercial success across Europe and the Americas. The company also announced that  former CEO Paul Kinnon will continue to serve on the Diadem SpA board and has been named Chairman of Diadem US, Inc.

Dr. Gerald Möller, Chair of Diadem’s Board of Directors, commented, “I am delighted that Michael will be leading Diadem at this exciting time for the company. Michael’s broad experience spans leadership roles in market development, sales and general management in our industry. His drive, skills and commitment have enabled him to successfully commercialize multiple innovative products. The growing number of therapeutic options for AD highlight the importance of identifying and monitoring Alzheimer’s patients early, with growing evidence that early interventions can slow disease progression. Our AlzoSure^® prognostic test can accurately identify individuals who will progress to AD years before the disease manifests. With Michael on board and Paul´s continued activities we will be optimally positioned for the upcoming growth phase of Diadem.

Mr. Rasche noted, “I am thrilled at the opportunity to lead Diadem as we move to rapidly commercialize the AlzoSure^® products—a truly innovative approach to improving the management of Alzheimer’s disease.  Diadem has already amassed an impressive amount of clinical data demonstrating the accuracy and utility of AlzoSure^® as a prognostic test for AD, and our research suggests additional applications as well. I look forward to working with our team and our partners to advance our business and ensure that the benefits of AlzoSure^® are widely available to relevant stakeholders around the globe.”

Michael Rasche has more than 30 years of leadership experience in high growth international healthcare and life sciences firms across Europe and the Americas. Most recently, he was Chief Commercial Officer at transformational diagnostics firm miDiagnostics. Previously Rasche was President and General Manager of International Business at Metabolon, where he oversaw operations and commercial activities during a period of very rapid growth. At Definiens, an AstraZeneca company, Rasche helped expand the business as Chief Commercial Officer, achieving 50% growth and setting the stage for major partnering agreements. He has also held leadership positions with Ayoxxa, Dako (now part of Agilent), Roche and Bayer Diagnostics.

Diadem’s AlzoSure^® Predict is a non-invasive biomarker blood test that can identify with high accuracy whether individuals over the age of 50 will experience significant cognitive decline due to Alzheimer’s disease up to six years before the onset of symptoms. Its utility is supported by clinical data from a large longitudinal study that was the basis for AlzoSure^® Predict’s CE-IVD marking clearance and a Breakthrough Device designation from the U.S. Food & Drug Administration. Diadem has formed a strategic collaboration granting Quest Diagnostics exclusive U.S. rights to the intellectual property of the AlzoSure^® Predict mass spectrometry assay for the purpose of developing, validating and marketing a laboratory-developed test service for U.S. providers and patients.

About AlzoSure^® Technology

AlzoSure^® Predict uses a proprietary antibody (U-p53^AZ) to measure blood levels of a conformational variant of the p53 protein that has been implicated in the pathogenesis of AD. The utility of AlzoSure^® Predict is supported by a large body of clinical data, including data from a longitudinal study that was the basis for AlzoSure^® Predict’s Breakthrough Device designation from the U.S. FDA and its CE-IVD marking in the E.U. AlzoSure^® Predict requires only 1mL of blood to detect the risk of Alzheimer’s disease at the asymptomatic and early symptomatic stage. In addition, the AlzoSure^® Predict products can identify “rapid progressors” at high risk of progressing to Alzheimer’s disease within two years. Diadem is also developing AlzoSure^® Confirm for the differential diagnosis of Alzheimer’s disease and other dementias. AlzoSure^® Confirm is a blood-based assay that uses a different set of protein fingerprints to measure levels of the unfolded p53 protein in order to distinguish between and predict whether or not individuals will decline to AD, frontotemporal dementia, Lewy body dementia or Parkinson’s disease-associated dementia. Clinical validation studies are underway.

About Diadem

Diadem was founded as a spin-out 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 has contributed to the lack of effective treatments for this devastating condition. As a result, patients have not been diagnosed until late in the illness, when effective treatment is less feasible. Diadem’s rapid, accurate and cost-effective AlzoSure^® Predict blood-based prognostic test makes it possible to identify patients early in the disease process, when effective interventions and better outcomes are potentially achievable. The utility of the approach has been demonstrated in longitudinal clinical studies that were the basis for awarding CE-IVD marking in the E.U. and a Breakthrough Device designation in the U.S. Additional retrospective and prospective clinical trials are ongoing to further validate clinical claims and support adoption and use. The company is also developing AlzoSure^® Confirm, a blood-based diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.co.uk.                

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Diadem SpA Announces Exclusive U.S. Licensing Agreement with Quest Diagnostics for Its AlzoSure® Predict Alzheimer’s Disease Prognostic Technology

—Quest to Develop and Market a Lab-developed Test Based on the IP of AlzoSure Predict® in the United States, Extending its Industry-leading Portfolio of Alzheimer’s Disease Blood Tests—

—Validating Clinical Data Suggests that AlzoSure® Predict’s Blood-Based Technology Can Help Identify Whether or Not Individuals Will Progress to Alzheimer’s Disease Up to 6 Years Before Diagnosis.

Milan, Italy and Secaucus, NJ — October 25, 2023 – Diadem SpA, (Diadem), a company developing one of the first blood-based tests for the early and accurate prediction of clinical progression to Alzheimer’s disease (AD), today announced that it has formed a strategic collaboration with Quest Diagnostics (NYSE: DGX), the nation’s leading provider of diagnostic information services, designed to improve access to high quality blood tests for evaluating the risk of Alzheimer’s disease.

Under terms of the agreement, Diadem has licensed exclusive U.S. rights to the intellectual property of its AlzoSure® Predict blood-based prognostic technology to Quest for the purpose of developing, validating and marketing a laboratory-developed test service for providers and patients in the U.S. Financial details of the agreement were not disclosed.

The U.S. Food and Drug Administration granted the AlzoSure® test Breakthrough Device Designation in January 2022. The test helps identify a variant of the p53 protein that is implicated in AD.

“Reliable, convenient and affordable blood tests are essential to the identification of AD risk in early stages, when interventions hold the greatest potential to slow disease progression,” said Kathleen Valentine, Vice President and General Manager, Neurology, Quest Diagnostics. “We are encouraged by the clinical research and FDA breakthrough designation for AlzoSure® and the opportunity to broaden quality and access to AD testing options supporting better patient care.”

“We are delighted to be working with Quest, an industry leader and innovator in novel prognostic and diagnostic tests for Alzheimer’s disease, to advance the development and commercialization of test options in the U.S. based on our AlzoSure Predict® technology,” said Paul Kinnon, Chief Executive Officer of Diadem. “The decade of work by our researchers and collaborators to clinically validate this important technology is bearing fruit as new therapies and growing knowledge about Alzheimer’s disease are providing hope that early interventions may slow or stop disease progression. We see AlzoSure® Predict as a potentially valuable contributor in this effort and view Quest as the ideal collaborator to help make the benefits of the AlzoSure® technology widely available to patients and their healthcare providers as part of Quest’s quality test portfolio.”

A large body of clinical data supports the utility of Diadem’s AlzoSure® Predict blood-based technology, suggesting it can help identify whether or not individuals over the age of 50 will experience significant cognitive decline due to Alzheimer’s disease up to six years before the onset of symptoms (area under the curve greater than 98%). Data presented at the Alzheimer’s Association International Conference in July 2023 confirmed the strong prognostic performance of AlzoSure® Predict based on longitudinal data from 479 individuals aged 60-85 who participated in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study.

This comprehensive dataset enabled evaluation of the performance of AlzoSure® Predict in assessing the risk that study participants would experience a significant cognitive decline to Alzheimer’s disease over time, and in identifying the timeframe during which this decline would occur (2 years for “rapid progressors” and 6 years for “slow progressors”).

More than 6 million Americans have Alzheimer’s, the most prevalent dementia, a number projected to reach 14 million by 2060. Conventional tests for Alzheimer’s involve specialist-delivered PET scans and cerebral spinal fluid testing in symptomatic individuals. New blood tests offer the potential for primary care physicians as well as specialists to identify people at risk for Alzheimer’s disease even before symptoms manifest.

Quest Diagnostics has a long-standing history of advancing diagnostic innovation in the field of dementia, including Alzheimer’s disease. The company’s AD-Detect™ portfolio features blood tests to evaluate risk associated with amyloid beta (AB) 42/40 proteins as well as ApoE genetic risk. The company’s AD-test services also include panels by cerebrospinal fluid (CSF) that help providers assess amyloid beta 42, tau and ApoE status. The company continues to explore the potential of other biomarkers for assessing AD risk that may complement its existing portfolio. For more information, visit Questforthecure.com.

About AlzoSure® Predict

AlzoSure® Predict is a non-invasive biomarker blood-based technology that uses a proprietary antibody (U-p53AZ) to measure blood levels of a conformational variant of the p53 protein that has been implicated in the pathogenesis of AD. The utility of AlzoSure® Predict is supported by clinical data from a large longitudinal study that was the basis for AlzoSure® Predict’s Breakthrough Device designation from the U.S. Food & Drug Administration and its CE-IVD marking in the E.U. AlzoSure® Predict requires only 1mL of blood to detect the risk of Alzheimer’s disease at the asymptomatic and early symptomatic stage. The AlzoSure® Predict technology can also identify individuals at high risk of progressing to Alzheimer’s disease within 2 years. Research has also demonstrated that AlzoSure® Predict can discriminate between the different kinds of dementia with high accuracy.

About Diadem

Diadem was founded as a spin-out 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 has contributed to the lack of effective treatments for this devastating condition. As a result, patients have not been diagnosed until late in the illness, when effective treatment is less feasible. Diadem’s rapid, accurate and cost-effective AlzoSure® Predict blood-based prognostic test makes it possible to identify patients early in the disease process, when effective interventions and better outcomes are now potentially achievable. The utility of the approach has been demonstrated in longitudinal clinical studies that were the basis for awarding CE-IVD marking in the E.U. and a Breakthrough Device designation in the U.S. Additional retrospective and prospective clinical trials are ongoing to further validate clinical claims and support adoption and use. Diadem is preparing for commercialisation of AlzoSure® Predict in collaboration with global strategic partners. The company is also developing AlzoSure® Confirm, a blood-based diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.co.uk.

This blog looks at all the factors that must be considered when determining a treatment pathway for patients, as well as the drugs used to treat those with AD.

So when making decisions about AD treatment, there are several important factors to be considered – is there sufficient support for the patient and caregiver, are there any adjustments for the environment needed including where they live, and who can support them during the treatment , are there any changes needed to the patient’s lifestyle, as well as addressing risk-factors of the treatment and providing AD-specific medications.

Current drugs used to treat AD

AD-specific medications include drugs which target brain neurotransmitter imbalance – these include choline esterase inhibitors (ChEi) and NMDA-receptor antagonists used both individually and in combination and are approved for the treatment of patients with established dementia.

In the past two years, the FDA has granted an approval, under an accelerated process, for two medications, which are based on antibodies to beta-amyloid, which is a toxic substance that accumulates in the brain of patients with AD. These treatments have received approval under an accelerated process.
These drugs were tested in large studies and initial analysis showed that patients that were on treatment deteriorated less than those on placebo. But these treatments are associated with amyloid-related imaging abnormalities (ARIA) in the form of brain edema and hemorrhage, and in rare cases, an increased risk of mortality.

On July 6, one of these medications, lecanemab (Lequembi) has received final approval from the FDA for the treatment of patients with mild cognitive impairment (MCI) and mild dementia. But before administration, patients should be tested for their ApoE status as the subtype ApoE4 is linked to a higher risk of ARIA. In addition, administration of lecanemab to patients who are receiving anticoagulation is also associated with an increased risk for ARIA in the form of brain hemorrhage
. Data from a large clinical trial with another medication of the same class, is very promising, with the expectation that it will also be approved soon.

References

[1] Aisen PS, Cummings J, Jack CR Jr, Morris JC, Sperling R, Frölich L, Jones RW, Dowsett SA, Matthews BR, Raskin J, Scheltens P, Dubois B. On the path to 2025: understanding the Alzheimer’s disease continuum. Alzheimers Res Ther. 2017 Aug 9;9(1):60. doi: 10.1186/s13195-017-0283-5. PMID: 28793924; PMCID: PMC5549378.

[1] Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, Holtzman DM, Jagust W, Jessen F, Karlawish J, Liu E, Molinuevo JL, Montine T, Phelps C, Rankin KP, Rowe CC, Scheltens P, Siemers E, Snyder HM, Sperling R; Contributors. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018 Apr;14(4):535-562. doi: 10.1016/j.jalz.2018.02.018. PMID: 29653606; PMCID: PMC5958625

[1] Atri A. The Alzheimer’s Disease Clinical Spectrum: Diagnosis and Management. Med Clin North Am. 2019 Mar;103(2):263-293. doi: 10.1016/j.mcna.2018.10.009. PMID: 30704681.

[1] https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval 

Diadem Presents Data at 2023 AAIC® Showing Its AlzoSure® Blood Test Can Identify Patients at High Risk of Significant Cognitive Decline Due to Alzheimer’s Disease

—Data from 479-Patient Study Confirms Strong Prognostic Utility of AlzoSure® Predict for Identifying Whether or Not Individuals Will Experience a Significant Cognitive Decline due to Alzheimer’s Disease (AD) Within a 2-Year or 6-Year Timeframe—

—Ability to Identify “Rapid Progressors” Who Will Develop AD Within 2 Years Is Especially Valuable Now that Treatments for Early AD are Available—AlzoSure^® Predict Can Facilitate Access to Effective Treatment for At-Risk Patients and Help Accelerate New Drug Research—

—Diadem Anticipates AlzoSure^® Predict Will Be Commercially Available in the U.S. in the Next 12 Months—

Milan, Italy and Amsterdam, Netherlands, July 19, 2023 – Diadem srl, a company developing the first blood-based test for the early prediction of clinical progression to Alzheimer’s disease (AD), today announced that study data being presented at the Alzheimer’s Association International Conference^® 2023 (AAIC^®) further strengthens the evidence supporting the prognostic value of Diadem’s AlzoSure^® Predict blood-based biomarker test, which can accurately identify whether or not individuals over the age of 50 will experience a significant cognitive decline due to AD years before the full onset of symptoms. The study data are included in a scientific poster¹ that is being presented today at AAIC^® 2023.

The Diadem AAIC^® 2023 analysis confirms the strong prognostic performance of AlzoSure^® Predict in AD based on longitudinal data from 479 individuals aged 60-85 who participated in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study. It is comprised of individuals who are cognitively normal or who have minimal cognitive impairment, as well as those with dementia due to Alzheimer’s disease or a non-AD source. This dataset includes comprehensive medical data on the participants, including blood samples collected over time. It allowed researchers to evaluate the performance of AlzoSure^® Predict in assessing the risk that study participants would experience a significant cognitive decline to AD over time, and in identifying the time frame during which this decline would occur (2 years for “rapid progressors” and 6 years for “slow progressors.”)

The performance of AlzoSure^® Predict in this study was high. For prediction of deterioration to AD within 2 years, the area under the curve (AUC) is 99.8%, and for decline to AD within 6 years, the AUC is 98.4%. AUC is a measure of the accuracy of a quantitative diagnostic test. A test with accuracy that is no better than chance has an AUC of 0.5, or 50%,  and a test with perfect accuracy has an AUC of 1, or 100%.

The cut-off values of AlzoSure^® Predict are defined to stratify individuals, at the time of testing, according to the time frame during which they may experience a significant cognitive decline. AlzoSure^® Predict showed high performance in identifying whether or not an individual was a rapid progressor who would cognitively decline to AD within 2 years, with a positive predictive value/negative predictive value (PPV/NPV) of greater than 90% and specificity of greater than 95%.

Diadem CEO Paul Kinnon noted, “These data further confirm AlzoSure^® Predict’s utility as a tool enabling personalized clinical decision-making with improved precision for AD that can be used by healthcare providers to identify whether or not a patient is at high risk of suffering cognitive decline to Alzheimer’s dementia in the coming 2 years or the coming 6 years. The opportunity to present clinical validation data for AlzoSure^® Predict at AAIC 2023 could not be more timely, as the recent FDA approval of lecanemab highlights the need for accurate and accessible screening tools to help providers and patients make informed treatment-related decisions. As an example, a physician will be better able to help patients and their families assess the trade-offs in choosing whether or not to take new disease-modifying drugs with potential side effects and substantial costs, with the knowledge of when a clinical deterioration to AD dementia is expected.”

Mr. Kinnon continued, “AlzoSure^® Predict also allows drug developers to screen, enrich and stratify patient populations to enhance clinical trials for new AD drugs. In particular, the ability to identify, in advance, the expected time-frame for cognitive decline will enable pre-hoc identification of sub-populations of interest and allow clinical researchers to enrich the study with patients with the desired rate of progression to AD.”

Mr. Kinnon concluded, “We expect to launch AlzoSure^® Predict in the U.S. within the next 12 months in partnership with a major diagnostics firm and look forward to working with healthcare decision-makers to ensure it is widely accessible to patients and their families.”

AlzoSure^® Predict is a non-invasive biomarker blood test that uses a proprietary antibody (U-p53^AZ) to measure blood levels of a conformational variant of the p53 protein that has been implicated in the pathogenesis of AD. The utility of AlzoSure^® Predict is supported by clinical data from a large longitudinal study that was the basis for AlzoSure^® Predict’s Breakthrough Device designation from the U.S. Food & Drug Administration and its CE-IVD marking in the E.U. AlzoSure^® Predict requires only 1mL of blood and 4 to 5 days for analysis to detect AD at the asymptomatic and early symptomatic stage. Previous research also demonstrated that AlzoSure^® Predict can discriminate between the different kinds of dementia with high accuracy.

1–The performance of AlzoSure^® Predict in stratifying the risk to experience a significant cognitive deterioration due to Alzheimer’s Disease, Sam Agus, Simona Piccirella, Leander Van Neste, Christopher Fowler, Colin L Masters, Jurgen Fripp, James D. Doecke, Daniela Uberti, Paul Kinnon, Alzheimer’s Association International Conference^® 2023, Poster #76902, July 19, 2023, 8:45am-4:15pm CEST.

About Diadem

Diadem was founded as a spin-out 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 has contributed to the lack of effective treatments for this devastating condition. As a result, patients have not been diagnosed until late in the illness, when effective treatment is less feasible. Diadem’s rapid, accurate and cost-effective blood-based prognostic test makes it possible to identify patients early in the disease process, when effective interventions and better outcomes are now potentially achievable. The utility of the approach has been demonstrated in longitudinal clinical studies that were the basis for awarding CE-IVD marking in the E.U. and a Breakthrough Device designation in the U.S. Additional retrospective and prospective clinical trials are ongoing to further validate clinical claims and support adoption and use. Diadem is preparing for commercialisation of AlzoSure^® Predict in collaboration with global strategic partners. The company is also developing AlzoSure^® Confirm, a blood-based diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.co.uk.

Identification and management of Alzheimer’s Disease (AD)

Dementia is common, especially in the aging population. More than 55 million people, around the world live with dementia.

Alzheimer’s Disease (AD) is the most common form of dementia. In the united states, more than 10% of the population, above the age of 75 have AD . This is clearly a huge global healthcare issue, with a significant impact on those, who struggle with it and on our society.
Memory decline is one of the most common signs of AD.

It is also a very common complaint, in the general (and mostly healthy) population.

In the US, as an example, nearly 10% of the population, aged 45 and above experiences subjective memory complaints (SCD). While SCD could be an early sign of AD and while signs of AD pathology are very prevalent in the older population, identifying the AD patients, before full dementia is manifest, is not a simple feat.

Cognition can be assessed by a variety of tools, some could be as simple as performing 3 simple tasks (e.g., the MinCog test), others are more elaborate and are part of a neuropsychiatric assessment. Most of these tests are not very sensitive to early deterioration, are dependent on the level of education of the patient and on the rater, can be expensive and not easily accessible.

Pathology is even more challenging. Cognitive decline can be caused by overall dysfunction, due to a physical or mental decline.  When it comes to neurodegenerative causes, such as AD, the pathology is occurring within the brain, segregated by the blood-brain-barrier, and therefore, very difficult to be identified.

Imaging studies, such as MRI and PET, are available, and are expensive, reader-dependent, and not easily accessible. Cerebrospinal fluid analysis is also possible and is less reader-dependent and expensive but is more invasive and as inaccessible as imaging studies.

Now, new blood tests are emerging, which provide a prediction as to the level of amyloid in the brain – a major, albeit not the only pathological hallmark of AD.

The treatment of AD includes lifestyle changes and treatment of risk factors, such as HTN and diabetes demands. These treatments are difficult to adhere to, but are very important, as AD is a slowly progressive and chronic disease. Once dementia settles in, medications that modulate the chemistry within the brain can offer a short-term symptomatic relief.

New medications, which aim to target the pathological process of AD and slow the progression of the disease, are now becoming available. In fact, 2 of them have already received a conditional approval in the US. These treatments seem to work better, when given before dementia if fully manifest, they are expensive, require facilities such as infusion canters, and come with a significant set of adverse effects, some of which could be life-threatening.

Diadem Reports New Data Showing Its AlzoSure® Predict Blood Test Can Accurately Identify “Rapid Progressors” Who Will Develop Alzheimer’s Disease Within Two Years

—New Computational Approach with PPV >95% Represents Another Significant Feature of AlzoSure® Predict Blood Test that Can Accurately Predict Whether Individuals Will Progress to Alzheimer’s Disease (AD) Up to Six Years Before Diagnosis—

—Identifying Rapid Progressors Who Will Develop AD Within 2 Years Will Be Especially Valuable with the Growing Availability of Drugs for Early AD, Enabling Access to Potentially Disease-Modifying Treatment and Facilitating New Drug Research—

Milan, Italy and San Francisco, California, January 9, 2023 – Diadem SpA, a company developing the first blood-based test for the early prediction of progression to Alzheimer’s disease (AD), today announced that its researchers have developed computational methods that enable its AlzoSure® Predict prognostic technology to accurately identify individuals who will rapidly progress to AD within two years’ time. More than 95% of the patients above the new computational “cutoff” used to define “rapid progressors” were shown to progress to AD within two years’ time, regardless of their baseline diagnosis. Using a modified form of the new approach, Diadem was able to do even better, accurately identifying a cohort where 100% of the patients progressed to AD within two years, while none of the patients not included in the modified cutoffcohort did so.

The computational analysis were developed using a relatively limited number of patient samples from major international longitudinal patient databases. The results will be further validated and expanded, and these analyses are already underway using global cohorts of qualified biological samples.

Diadem CEO Paul Kinnon noted, “We believe that this new refinement of our AlzoSure® Predict test could not be more timely, as last week’s FDA approval of lecanemab, which shows promising signs of slowing cognitive decline in early AD, highlights the need for accurate and economical screening tools to select patients most likely to benefit from early treatment. The cost benefit trade-off in choosing whether or not to take these drugs, with their potential side effects and high costs, is shifted when a patient is identified by AlzoSure® Predict’s new computational cutoff as having a high probability of advancing to AD in just two years’ time. The additional feature should also be valuable for drug development, since it will allow researchers to select “rapid progressor” patients for clinical testing who are almost certain to develop AD within two years, enabling a much faster and more cost-effective read-out of clinical trial results.”

Diadem is currently expanding its initial confirmatory studies of the new computational cutoff. It plans to present data on its results at scientific meetings later this year. The company is also planning for the commercial launch of AlzoSure® Predict in the U.S. this year, in collaboration with a major diagnostics partner.

AlzoSure® Predict can allow drug developers to screen, enrich and stratify patient populations to facilitate Alzheimer’s disease clinical trials. Use of the test enables researchers to identify with high confidence individuals who will experience a decline to Alzheimer’s dementia years in advance of diagnosis .

Clinical studies show that AlzoSure® Predict is able to predict cognitive decline to AD dementia with an AUCgreater than 90%, regardless of the cognitive, amyloid or tau status of the patient at the time of testing.AlzoSure also has demonstrated superiority compared to Pib-PET amyloid imaging in predicting decline to AD dementia in patients before, or with, early signs of cognitive deficits. The company is in the final stages of further validating its earlier findings using longitudinal data from the U.S.-based Alzheimer’s Disease Research Centers (ADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts.

AlzoSure® Predict is a non-invasive biomarker blood test that can identify with high accuracy whether individuals over the age of 50 with signs of cognitive impairment will or will not progress to Alzheimer’s disease up to six years before diagnosis. AlzoSure® Predict uses a proprietary antibody (U-p53AZ) 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 diagnostic and as a predictive biomarker to identify individuals likely to progress to AD up to six years before symptoms appear.

The utility of AlzoSure® Predict is supported by clinical data from a large longitudinal study that was the basis for AlzoSure® Predict’s Breakthrough Device designation from the U.S. Food & Drug Administration and its CE-IVD marking in the E.U. AlzoSure® Predict requires only 1mL of blood and 4 to 5 days for analysis to detect AD at the asymptomatic and prodromal (early symptomatic) stage, with an accuracy greater than 95% up to at least 6 years in advance of the clinical onset of symptoms. Previous research also demonstrated that AlzoSure® Predict can discriminate between the different kinds of dementia with high accuracy.

About Diadem

Diadem was founded as a spin-out 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 longitudinal clinical studies that were the basis for awarding CE-IVD marking in the E.U. and a Breakthrough Device designation in the U.S. Additional retrospective and prospective clinical trials are ongoing to further validate clinical claims and support widespread adoption and use. Diadem is preparing for commercialisation of AlzoSure® Predict in collaboration with global strategic partners. The company is also developing AlzoSure® Confirm, a blood-based diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.co.uk.

At CTAD 2022 Diadem Highlights How Its AlzoSure® Predict Prognostic Blood Test for Alzheimer’s Disease Will Help Patients and Facilitate Development of New Therapies

—Data Presented at CTAD Conference Shows that AlzoSure® Predict Can Accurately Identify Stage of Cognitive Decline and Predict Whether or Not Individuals Will Progress to Alzheimer’s Disease Up to Six Years Before Diagnosis, Supporting Early Treatment with the Potential to Slow Disease Progression—

—As a Simple and Economical Blood Test, AlzoSure® Predict Will Be Widely Accessible to Physicians and Individuals/Patients and Suitable for Use by Drug Developers for Improved Clinical Trials—

—Growing Body of Evidence Confirming the Prognostic Accuracy of AlzoSure® Predict Sets the Stage for U.S. Commercialization Starting in Early 2023—

Milan, Italy and San Francisco, California, December 5, 2022 – Diadem SpA, a company developing the first blood-based test for the early prediction of progression to Alzheimer’s disease (AD), presented clinical data at the 15^th Clinical Trials on Alzheimer’s Disease (CTAD) conference highlighting the accuracy and clinical utility of its AlzoSure^® Predict prognostic blood test for Alzheimer’s Disease (AD), setting the stage for commercialization in the U.S. beginning in 2023.

In the presentation by Diadem Chief Medical Officer Dr. Sam Agus on December 2^nd, Diadem discussed how AlzoSure^® Predict can aid pharmaceutical and biotechnology companies for screening, enrichment and stratification of patient populations to facilitate Alzheimer’s disease clinical trials. Use of the test enables drug developers to identify individuals who will experience a decline to Alzheimer’s dementia up to six years in advance of diagnosis with high confidence, regardless of their cognitive, amyloid, or tau measurement status at the time of testing. This type of patient stratification can improve clinical trial recruitment and the odds of success, as it ensures that patients participating in the trials have a very high probability of developing full-blown AD.

Additionally, Dr. Agus discussed the utility of the test as a screening tool to enable physicians and patients to identify those at high risk of developing AD very early in the disease process, when therapies may be most effective. The likely approval of new drugs such as lecanemab from Eisai and Biogen, which shows promising signs of slowing cognitive decline in early AD, highlights the need for accurate and economical screening tools to select patients most likely to benefit from early treatment.

“This is an exciting time in the battle against Alzheimer’s disease,” said Paul Kinnon, CEO of Diadem. “Advances in AD diagnosis and therapies are finally providing hope that we can begin to slow or stop the progression of this terrible disease that impacts so many individuals and families. We see AlzoSure^® Predict playing a key role in this progress, with its wide potential accessibility and its ability to enhance AD clinical trials and to identify individuals at high risk for progression to AD. As we expected, global market research we are in the process of conducting is showing that both individuals and physicians indicate strong interest in early access to better diagnostic tools for Alzheimer’s.”

Mr. Kinnon continued, “Our studies show that AlzoSure^® Predict is able to predict cognitive decline to AD dementia with an AUC greater than 90%, regardless of the cognitive, amyloid, or tau status of the patient at the time of the test. AlzoSure also showed superiority compared to Pib-PET amyloid imaging in predicting decline to AD dementia in patients before, or with, early signs of cognitive deficits. We now are in the final stages of further validating these findings using longitudinal data from the U.S.-based Alzheimer’s Disease Research Centers (ADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohorts, and look forward to releasing results in the coming months. We also are preparing for the commercial launch of AlzoSure^® Predict in the U.S. in the new year, in collaboration with a major diagnostics partner.”

AlzoSure^® Predict is a non-invasive biomarker blood test that can identify with high accuracy whether individuals over the age of 50 with signs of cognitive impairment will or will not progress to Alzheimer’s disease up to six years before diagnosis. AlzoSure^® Predict uses a proprietary antibody (U-p53^AZ) 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 diagnostic and as a predictive biomarker to identify individuals likely to progress to AD up to six years before symptoms appear.

The utility of AlzoSure^® Predict is supported by clinical data from a large longitudinal study that was the basis for AlzoSure^® Predict’s Breakthrough Device designation from the U.S. Food & Drug Administration and its CE-IVD marking in the EU. AlzoSure^® Predict requires only 1mL of blood and 4 to 5 days for analysis to detect AD at the asymptomatic and prodromal (early symptomatic) stage, with an accuracy greater than 95% up to at least 6 years in advance of the clinical onset of symptoms. Previous research also demonstrated that AlzoSure^® Predict can discriminate between the different kinds of dementia with high accuracy.

About Diadem

Diadem was founded as a spin-out 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 longitudinal clinical studies that were the basis for awarding CE-IVD marking in the E.U. and a Breakthrough Device designation in the U.S. Additional retrospective and prospective clinical trials are ongoing to further validate clinical claims and support widespread adoption and use. Diadem is preparing for commercialisation of AlzoSure^® Predict in collaboration with global strategic partners. The company is also developing AlzoSure^® Confirm, a blood-based diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.mywebpreview.co.uk/.

Diadem Builds Out Executive Team As It Prepares for Commercialization of Its AlzoSure® Predict Prognostic Test for Alzheimer’s Disease

—Diadem to Participate in the 15th Clinical Trials on Alzheimer’s Disease (CTAD) Conference—

Milan, Italy, November 21, 2022 – Diadem SpA, (or Diadem US, Inc.) a company developing the first blood-based test for the early prediction of progression to Alzheimer’s disease (AD), today announced key additions to its senior management team. Sam Agus, MD, has been appointed Chief Medical Officer (CMO), James Clark, PhD, has been named Head, External Affairs and Collaborations, and Peter Bream is Diadem’s new Chief Financial Officer (CFO). They join Simona Piccirella, PhD, Vice President of Operations and Development and Chief Executive Officer Paul Kinnon at Diadem.

Separately, the company announced that it will participate in the upcoming 15^th Clinical Trials on Alzheimer’s Disease (CTAD) conference being held November 29-December 2, 2022 in San Francisco. Diadem will present, U-p53AZ in prognostication of early onset Alzheimer’s disease up to 6 years in advance of the clinical diagnosis, in a Late Breaking Oral Communication Session at 4:20 pm on Friday, December 2^nd. The company will also participate in a CTAD Task Force on Blood Biomarkers roundtable “Point of View from the Assay Industry” discussion on November 29 from 9:55 to 10:25 am.

“We are pleased to welcome these highly experienced executives to Diadem as we prepare for the commercialization of our revolutionary AlzoSure^® Predict blood test that can accurately identify whether or not an individual will progress to Alzheimer’s as much as six years before symptoms of the disease are apparent,” said Mr. Kinnon. “Sam, James and Peter are seasoned executives with decades of success in building and leading pharmaceutical, diagnostics and life science organizations. Simona has already played a major role in growing Diadem and developing the AlzoSure technology to this stage. Their contributions will be instrumental as we prepare for the commercialization of AlzoSure^® Predict in the new year.”

Mr. Kinnon continued, “We also welcome the opportunity to participate in several sessions at the upcoming CTAD conference, one of the year’s most important Alzheimer’s scientific meetings. This is an excellent opportunity to continue our campaign of educating AD researchers, clinicians and drug developers about the potential of AlzoSure^® Predict to help transform the diagnostic and therapeutic landscape of Alzheimer’s disease.”

Mr. Kinnon concluded, “Dr. Agus’s expertise will be very helpful as we conduct additional clinical trials to further validate the diagnostic utility of AlzoSure^® Predict and to facilitate obtaining regulatory approvals, as well as to help us strengthen the critical relationships with the medical community that will be essential for its widespread adoption and use. We expect to establish additional partnerships and collaborations to accelerate the commercial and clinical availability of this important  advance, and Dr. Clarke’s long-standing relationships throughout the industry will be invaluable to this effort. Dr. Piccirella’s combination of scientific acumen and organizational skills will continue to be central to the continued evolution of the company. Finally, every successful company in our sector requires a first-rate CFO who appreciates the complexity of the healthcare ecosystem, and we are fortunate to have Peter coming onboard as a core member of our team. I enthusiastically welcome them to Diadem.”

CMO Sam Agus, MD is a board-certified neurobiologist with more than 20 years of global experience in multiple therapy areas. He has served as a senior leader in clinical development and medical affairs at pharmaceutical companies, such as Lundbeck, Shire, Abbott, Solvay and Teva, and as CMO at a number of biotechnology firms. His experience spans clinical, medical, and regulatory strategy, multidisciplinary team leadership, portfolio management, clinical trial design and execution, regulatory strategy, product launches, and market access. Additionally, Dr. Agus has taken an active part in public-private partnerships, collaborations and business alliances, and in completing a number of financing rounds.

Head of External Affairs and Collaborations James Clarke, PhD, has more than 20 years of leadership experience as a senior executive in pharmaceutical, diagnostic and precision medicine companies of varied sizes, phases of development and geographies. He has led R&D units, managed certified laboratories in the US and UK, overseen special projects, and has successfully developed and commercialized more than 15 global diagnostic products.  Dr. Clarke earned a PhD degree from Glasgow University.

CFO Peter Bream has over 35 years of experience in international business including serving as chief financial officer of public companies in the medical diagnostics, pharmaceuticals, engineering, and chemical sectors. Most recently he was CFO of two Cambridge-based genomics start-ups and was a non-executive director and board committee member for a listed healthcare business. Mr. Bream has a degree in Engineering and Management from Cambridge University and is a Chartered Accountant.

Vice President Operations and Development Simona Piccirella, PhD, is an experienced researcher and business manager with deep  knowledge of the life sciences sector. She co-founded the company VisMederi srl, where she was chief operating officer until 2016, serving clients such as Sanofi, Novartis, Glaxo SmithKline and Takeda in immunogenicity evaluations of biologics and analytical assay validation. Dr. Piccirella earned a degree in Natural and Biological Sciences and a PhD in Molecular Medicine from the University of Siena.

AlzoSure^® Predict is a non-invasive biomarker blood test that can identify with high accuracy whether individuals over the age of 50 with signs of cognitive impairment will or will not progress to Alzheimer’s disease up to six years before diagnosis. AlzoSure^® Predict uses a proprietary antibody (U-p53^AZ) 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 diagnostic and as a predictive biomarker to identify individuals likely to progress to AD up to six years before symptoms appear.

The utility of AlzoSure^® Predict is supported by clinical data from a large longitudinal study that was the basis for AlzoSure^® Predict’s Breakthrough Device designation from the U.S. Food & Drug Administration and its CE-IVD marking in the EU. AlzoSure^® Predict requires only 1mL of blood and 4 to 5 days for analysis to detect AD at the asymptomatic and prodromal (early symptomatic) stage, with an accuracy greater than 95% up to at least 6 years in advance of the clinical onset of symptoms. Previous research also demonstrated that AlzoSure^® Predict can discriminate between the different kinds of dementia with high accuracy.

About Diadem

Diadem was founded as a spin-out 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 longitudinal clinical studies that were the basis for awarding CE-IVD marking in the E.U. and a Breakthrough Device designation in the U.S. Additional retrospective and prospective clinical trials are ongoing to further validate clinical claims and support widespread adoption and use. Diadem is preparing for commercialisation of AlzoSure^® Predict in collaboration with global strategic partners. The company is also developing AlzoSure^® Confirm, a blood-based diagnostic test for AD that has shown promising results in early studies. For more information, visit diademdx.mywebpreview.co.uk/.