Dementia/Alzheimer Drug Attributed to Cystatin-C and other mutations – precision medicine drug development

Project Information

DNACA

Grant agreement ID: 190174464

DOI

10.3030/190174464

Project closed

EC signature date 5 April 2023

Start date 1 March 2023

End date 28 February 2025

Funded under

• The European Innovation Council (EIC)

Total cost

€ 3 571 875,00

EU contribution

€ 2 500 000,00

Coordinated by

ARCTIC THERAPEUTICS EHF
Iceland

Periodic Reporting for period 2 - DNACA (Dementia/Alzheimer Drug Attributed to Cystatin-C and other mutations – precision medicine drug development)

Reporting period: 2024-03-01 to 2025-02-28

Summary of the context and overall objectives of the project

The objective of the project is the development of an effective treatment for rare and common forms of dementia, commencing with a drug addressing Hereditary Cystatin C Amyloid Angiopathy (HCCAA), caused by a genetic mutation, transitioning into other amyloid-induced forms – including Alzheimer’s (AD). The WHO estimates that over 55 million people are living with dementia worldwide, a figure that will continue to rise in the absence of effective treatments, resulting staggering socio-economic costs of €2.8 trillion by 2030. Current and emerging amyloid-tackling treatments include serious, and sometimes fatal side effects, and adoption across the healthcare system has been very slow as a result. AT has developed AT-001, a new-chemical entity (NCE) oral treatment that removes the challenges faced by other amyloid therapies, with our research demonstrating the ability to prevent to formation of toxic oligomers causing damaging amyloid aggregation into the brain – therefore for not only delaying the onset of dementia but preventing it. AT-001 has been developed through the DNACA precision-medicine based platform, which applies big data mining and deep learning/AI algorithms to identify patients with validated biomarkers. AT-001's clear differentiation is further underlined by strong signals that it also prevents aggregation of tau proteins, common in many types of dementia. Completed Phase IIA clinical trial showed strong effects for treatment of HCCAA and AT has now entered into a registration study to bring the compound to market in early 2026, following an approval from the European Medicines Agency (EMA), further informing the treatment of Alzheimer’s (AD) - which accounts for 60% of all dementia cases – potentially changing the lives of millions of people for the better, increasing their quality of life and sharply reducing the downstream costs of the world’s healthcare systems.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Last year, AT secured approval from EMA for the initiation of an Investigational Medicinal Product (IMP) registration study targeting Hereditary Cystatin C Amyloid Angiopathy (HCCAA). This approval is not just a pivotal step for us but also lays the groundwork for extending our research into more common forms of dementia, including AD. The Phase IIb/III clinical trial for AT-001 in HCCAA has successfully reached its one-year mark. Enrollment was completed in December 2024, with 15 patients enrolled from the original target cohort of up to 25. The trial follows an open-label, single-arm protocol with dosage escalation based on tolerability and biomarker response. Throughout the study, patient safety has remained a top priority, with scheduled Data Safety Monitoring Board (DSMB) reviews confirming adherence to safety protocols. No major safety concerns have been reported, and all patients remain actively engaged in the study. Preliminary biomarker analysis suggests modulation trends consistent with the expected therapeutic mechanism of AT-001, though full statistical evaluation will be conducted at the trial’s completion. All safety and observable efficacy measures appear strong, and the study remains on track with no major deviations. The final patient is expected to complete 12 months of treatment by the end of the year, at which point the full safety and efficacy dataset will be analyzed to support further clinical and regulatory decisions. AT firmly believes this will result in a market approval in Iceland to treat HCCAA, as well as opening the possibility of off-label prescription for other forms of familial dementia in Europe, anchored by the strong safety profile of the treatment.

AT’s commercial model is geared towards partnering with an established pharma major to bring the AT-001 to market, tapping into the experience and infrastructure of a leading player driving consolidation in the wider therapeutic area (TA). We strongly believe that it is extremely important to demonstrate a clear differentiation from approved and emerging rival treatments ahead of any out-licensing agreement. This will put AT in a much stronger position to secure and negotiate a more favorable out-licensing agreement with partners to take our assets the last mile to market. It is important to note that we are defining our competition from an asset perspective – not from a company perspective, since both Biogen and Lilly are possible co-development partners, despite having competing assets approved in certain geographies. This work is progressing well, and we have identified all major approved and emerging competing assets from information available in the public domain, as well as shaping the differentiation based on our business intelligence work.

1. We have commenced soft outreach via our proprietary network, as working towards aligning our value proposition across online and offline channels and material. This includes a revamped website, with messaging geared towards BD&L teams at possible pharma partners consolidating or investing in our core therapeutic areas (TA). When completed, this sharpened messaging will be amplified via digital channels to generate inbound conversations, providing air cover ahead of direct outreach.
2. The news of the closing of our oversubscribed €26.5 million Series A financing was widely reported across top-tier trade, tech, and financial publications, including Endpoints and Bloomberg. This heightened exposure has led to an influx of inbound interest and discussions – not only around our frontrunners but also across our broader portfolio. Regarding AT-001, we have already started to engage with pharma majors on a possible collaboration – including Roche/Genentech and Merck & Co (MSD Group in North America).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

There is a consensus emerging across the scientific community that amyloid and tau protein plagues are the major causes of dementia, including AD. This is not only triggering new treatments, targeting protein plaques, but also early diagnostics tools – such FDA-breakthrough status blood tests, measuring the accumulation of these proteins in plasma to predict the onset of dementia. But challenges remain. Immunotherapies, such as Biogen’s lecanemab, have serious and sometimes fatal side effects, in-clinic administration via IV presents a clear adoption and adherence hurdle, crossing the blood-brain barrier (BBB) remains a challenge and efficacy hinges on early detection. AT-001 is an oral treatment that is being developed to tackle those challenges by safely crossing the BBB, demonstrating no serious side-effects and coupled with advances in early detection, patients can remain on the drug indefinitely. AT-001 goes beyond current and emerging treatment since it also targets tau, AT's research shows. It is widely understood that dementia is under-diagnosed, partly because of the lack of safe and effective treatments and that the patient population goes well beyond the WHO estimate of 55 million people. The socio-economic impact associated with dementia is expected to reach €2.8 trillion by 2030 and this will continue to rise without safe and effective treatment, reversing this devastating trend. The current market of dementia drugs is in the region of €20 billion and based on conservative forecasting, AT-001 has the potential to carve out a €2 billion market share – and even expand the current market size, historically limited by the absence of safe and effective treatments.

Articles

AT-001 Breaks down protein aggregates