CDP-13: [Funding] Arctic Therapeutics

One liner: Arctic Therapeutics is accelerating treatments for millions of patients by harnessing the power of applied genomics to guide drug development. Its lead compound, AT-001, targeting HCCAA and Alzheimer’s Disease is of particular interest to Cerebrum DAO.

Cerebrum DAO Deal Team

Peer Review Evaluation: A translational neuroscience expert, a neuroscience academic, an industry professional Project Lead: Maryna Polyakova Project Squad: Brian Magierski, Tuan Dinh, Peter Groenen, Eleanor Davies Sourcer: Maryna Polyakova

Project Team

Founder and Chief Medical Advisor: Dr. Hakon Hakonarson MD, PhD Co-Founder & CEO: Ivar Hakonarson Chief Strategy Officer: Gulli Arnason

Summary Deal Analysis

Arctic Therapeutics (AT) is a drug development company, rooted in applied genomics. AT is a close collaborator of the Center for Applied Genomics (CAG), one of the world’s most respected genomic research institutions. AT is raising €12.5M in new equity from investors to advance its drug pipeline of five treatments, specifically its frontrunners, AT-001 and AT-004.

The asset AT-001 has been approved by the European Medicines Agency (EMA) for a registration study for a rare form of familial dementia, transitioning into more common forms – including Alzheimer’s. The candidate has demonstrated positive results in Phase IIa clinical trial for Hereditary Cystatin C Amyloid Angiopathy (HCCAA). AT-004 is being prepared for a Phase IIa study to treat acne vulgaris, with plans to expand into other inflammatory skin diseases – such as atopic dermatitis and psoriasis.

AT-001 is of specific interest to the Cerebrum DAO community. This proposal, therefore, is to ask the Cerebrum DAO community, regarded by the AT team for its strong value alignment in neurodegenerative disease research, for its support in bringing the candidate to the clinic.

Problem

An estimated 55 million patients globally are living with dementia, with an additional 10 million diagnosed with the disease annually. According to the World Health Organisation, dementia is currently the seventh leading cause of death globally, and one of the major causes of disability and dependency among older people. In 2019, dementia cost economies globally USD $ 1.3 trillion. Approximately 50% of these costs are attributable to care provided by informal carers (e.g. family members and close friends). Estimated dementia-related costs are expected to reach a staggering €2.8 trillion by 2030. Dementia, including Alzheimer’s, affects millions worldwide, causing cognitive decline and loss of independence. It is a progressive, debilitating condition with no known cure and the number of cases is rapidly increasing due to increasingly ageing populations. Women are disproportionately affected by dementia, both directly and indirectly, experiencing higher disability-adjusted life years and mortality due to dementia, but also providing 70% of care hours for people living with dementia.

Despite these staggering statistics and the personal, social, and economic toll of dementia, current treatments only manage symptoms without addressing the underlying causes or halting disease progression. This critical gap in effective therapies underscores the pressing need for transformative treatments that can potentially modify the course of the disease, improve patients' quality of life, and alleviate the growing burden on healthcare systems and caregivers worldwide.

Solution

Arctic Therapeutics is developing its frontrunner treatment, AT-001. It is a second generation molecule, generated as a new chemical entity (NCE) via a repurposing approach. AT holds exclusive rights to develop the IP portfolio related to this treatment and in the field of neurodegeneration, as well as patents for other lead candidates in its pipeline.

AT-001 breaks up clumps of amyloid that have deposited in the brain and vessel walls, and has shown a strong signal in biomarkers capturing reduction in amyloid protein aggregation. So far, the treatment has demonstrated successful Phase IIa clinical trial data with the first patient, diagnosed with Hereditary Cystatin C Amyloid Angiopathy (HCCAA). Evidence from the study showed a transition from progressive amyloid angiopathy with strokes to a marked improvement with signs of reduced Amyloid-Cystatin C depositions in the skin, with no further life threatening strokes. Notably, there were no significant new stroke/cardiovascular events, 50-95% skin deposits reduction was observed, and no disease progression was noted, demonstrating potential for disease prevention.

AT-001 is an oral treatment, which removes challenges faced by other amyloid protein therapies for dementia, including serious side-effects and blood-brain barrier penetration problems. Its unique mechanism of action (MOA) not only removes amyloid plaques, which have aggregated in the brain, but also prevents the formation of toxic oligomers. This is achieved by reducing disulfide bonds, the structural elements that maintain these detrimental protein structures. In vitro data also suggests that the treatment may have a similar effect in preventing tau tangles.

Opportunity

Arctic Therapeutics presents a significant opportunity in the €1.4BN Serviceable Addressable Market for familial dementia and Alzheimer's treatments. AT-001 has shown promising results in breaking up Cystatin-C-amyloid deposits, demonstrating efficacy in its first patient with early-onset HCCAA. This positions the company to potentially capture a substantial portion of the €2.1BN Serviceable Obtainable Market, addressing a critical need in dementia treatment.

Relevance to Cerebrum DAO

Cerebrum DAO aims to identify, fund and support the development of promising research and translational projects to accelerate the development of new treatments for Alzheimer's disease and related dementias.

AT-001 has already been tested in a 24-month Phase I/II study in patients with retinitis pigmentosa associated with Usher syndrome. The highest safe dose was set at 500mg/day. (Clinical efficacy has not been definitively established.) Currently a biomarker clinical study is planned in selected Alzheimer’s Disease patients. At present, only in vitro and animal model in vivo studies support the efficacy of AT-001 in reducing amyloid plaques.

The Blood-Brain Barrier penetration capability of AT-001 allows to hypothesise that the compound may act similarly to disassemble amyloid plaques in the brain. Previous applications and clinical trials have partially de-risked the compound’s profile for patients. Given this data, the Phase III clinical trial of AT-001 is aligned with Cerebrum DAO’s mission to find a potential cure for dementia.

IP Roadmap

Arctic Therapeutics holds the exclusive licence for applications of AT-001.

Financing and Cerebrum DAO Terms

AT is actively seeking funding to propel their research forward. They recognize the value that Cerebrum DAO and its members bring, both in terms of financial support and expertise. They are offering an opportunity for Cerebrum DAO members to provide €75,000 in funding. AT is raising a minimum of €20M and has also secured non-dilutive funding. AT is expecting the close of the round in mid-October.

Key Leadership

● Dr. Hakon Hakonarson, Chief Medical Advisor: Founder of AT and one of the world’s leading authorities in the field of applied genomics and translational research. ● Ivar Hakonarson, Chief Executive Officer: Co-founder of AT ● Lisa DeMarco, Chief Business Officer: Ex-GSK, with over 25 years of experience in the pharmaceutical industry ● Asbjorn Kristbjornsson, Chief Information Officer: 20 years of expertise, specialising in building laboratory management systems and leading genotyping and sequencing projects ● Gulli Arnason, Chief Strategy Officer: A venture-building veteran, who positioned digital health company Sidekick as one of the world’s leading players ● Dr. Asbjorg Osk Snorradottir, Director of Clinical Development: The world's leading expert on Hereditary Cystatin C Amyloid Angiopathy (HCCAA), having devoted the last 18 years to finding an effective treatment. ● Dr. Charlly Kao, Chief Scientific Officer: An immunologist and scientist by training. Has played a key role in the design and execution of the proof-of-concept studies that have advanced AT’s wider drug portfolio.

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Please visit the following link to view the full proposal, as the proposal content exceeds Snapshot's character limit: https://docs.google.com/document/d/1e8-exO4J856r6dAKO6g4gIJa8tYYPpFHKrD5zAUHe9I/edit?usp=sharing