2023-12-010 - VariantX_Patent - IP rights related to a novel gene-therapy based product as a key tool in the treatment of liver-related diseases

VariantX_Patent

2023-12-010

VariantX is a potential novel gene-therapy for the treatment of ER-stress related disease in the liver. Variant X will firstly focus on two rare diseases with insufficient treatments that are most likely to benefit from amelioration of the ERstress symptoms

IRB Barcelona adheres to the 3 pillars of ESG, environmental, social and governance, to perform all of their projects with the highest standards.

VariantX focuses in rare disease with unmet medical needs. If successful, it will reduce by healthcare costs and Increase quality of life in rare-diseases with ER-stress associated patients and their families. It will also bring new treatments to patients without it or with extremly limited options.

ER-stress plays a key role in the development of a broad number of diseases of different etiologies with genetic and metabolic origins (diabetes, cardiovascular, cancer, aging, neurodegenerative diseases), either as a primary cause of disease or as a secondary pathological phenomenon. The effective resolution or amelioration of ER-stress holds significant potential as a single or combined therapy for rare diseases lacking an efficient treatment. VariantX will firstly focus on Alpha-1 AntiTrypsin Disease (AATD), a rare disease with high unmet medical need, making it attractive to companies and investors in the area of rare diseases. Furthermore, if successful, VariantX gene therapy has the potential to be extended for the treatment of additional ER-related diseases, such as Cystic fibrosis, another rare disease we have started exploring. Our solution, VariantX, is a novel gene therapy that introduces a unique gene variant designed to restore ER homeostasis. This innovative, monogenic, and non-replacement approach directly targets and resolves ER stres and has already been validated in human AATD in vitro models and in murine in vivo liver disease models. Operating via a Dual Mechanism, VariantX uniquely addresses the pathology in AATD by potentially disaggregating accumulated liver protein and facilitating the release of active, functional protein (demonstrated in vitro). A Key Differentiator of this therapy, particularly for AATD, is its dual benefit: it not only aims to address and reverse liver damage but also actively promotes the release of functional protein. This dual action significantly sets it apart from current protein augmentation therapies and siRNA approaches, a crucial distinction recently highlighted by a leading Key Opinion Leader (KOL) in AATD. This positions it as a potential breakthrough for a range of ER-stress related conditions.

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Our first approach is the creation of a spin-off company to attract private funds in order to develop the technology at least until Clinical Phase 1.

The unmet medical needs in ER stress are profound as current treatments largely fail to target the root cellular dysfunction. This means many diseases driven by ER stress lack effective, disease-modifying therapies, leaving systemic issues unaddressed. Within this critical area, Alpha-1 Antitrypsin Deficiency (AATD) serves as a compelling example. This rare inherited disorder, affecting approximately 1 in 2,000 to 5,000 newborns, is fundamentally caused by the accumulation of misfolded A1AT protein, which directly triggers and perpetuates ER stress, particularly in the liver. Intravenous infusion of A1AT, also known as augmentation therapy, is the only specific treatment available for AATD. Though augmentation therapies have become the gold standard for managing AATD, they are invasive, partially effective, require the assistance of a medical professional, and only address lung-associated manifestations. Fruthermore, the leading therapy in pipeline, based on siRNA, only targets liver damage, while, gene-editing approaches like CRISPR are still deemed too high risk by clinicians.

The broad prevalence of ER-stress across numerous disease indications presents a significant and expansive market opportunity. Our market scope spans from a TAM of $12 billion for those ER-stress related conditions we have prioritized (mainly rare diseases), including AATD, Cystic fibrosis, Wolfram Syndrome and Alport Syndrome. Within this substantial market, our starting strategic entry point is AATD, estimated at $1.8 billion (SAM). We are considering a market penetration focused on severe liver complications, translating to $180 million. All market figures are derived from the GlobalData database and calculated across the 7 Major Markets (7MM): the United States, Germany, France, Italy, Spain, the United Kingdom, and Japan.

We have calculated a need of 2-5M € for the prototype and preclinical development as well as an additional 5-10M€ for the Clinical Phase 1.

Grants to cover the prototype set up and validation as well as investors and/or pharmaceutical companies willing to enter into co-development or in-licensing agreements to futher develop the product to reach the market.

1) Cell-base validation for AATD - done 2) In vivo validation and cell-base validation for AATD - done 3) VariantX vector prototype 4) VariantX vector validation 5) Optimization 6) Preclinical phase 7) Clinical phase I

We have discovered new gene variants with the potential to reverse the ER-stress symptoms and the associated pathological alterations. Prelimnary in vivo mouse validation in place.

Gene therapies have recently reached the market. The elevated costs per treatment are both, barrier and drivers for pharmaceutical companies. Furthermore, the R+D cost are still above the ones for small molecules.

1) Mature the technology until prototype validation 2) Establishment of a spin-off company to secure additional funding until Clinical Phase 1 3) Licensing the product (or merge) with a pharmaceutical company to complete the clinical development until reaching the market

PCT extension filed in July 2024. National phases are expected to be in the end of 2025.

Coonwership agreement in place.

Know-how and expertise of the scientific team in ER-stress and mitochondria area

For the devolpment of the VariantX project, all main fundamental ethical codes will be taken into account as well as implemented following internal policies and regulations at IRB Barcelona, such as Code of Conduct, Conflict of Interest Policy, Recruitment Policy, and Equality Plan as well as the Regulations on IPR and Spin-off creation.

The effective resolution or amelioration of ER-stress holds significant potential as a single or combined therapy for rare diseases lacking an efficient treatment. In this sense, Variant X will firstly focus on two rare diseases with insufficient treatments that are most likely to benefit from amelioration of the ERstress symptoms as well as attractive for companies and investors in this area. Furthermore, if successful, VariantX gene therapy has the potential to be extended for the treatment of additional ER related diseases.