2024-13-002 - APP1B - A novel therapeutic that halts progression of Alzheimer Disease by acting on a previously untapped target

APP1B

2024-13-002

A non-amyloid drug that targets a mechanism common to several subtypes of Alzheimer's disease (AD). An innovative therapy consists of a monoclonal antibody that binds to the amyloid precursor protein (APP), thereby preventing the formation of Aβ plaques (the pathological hallmark of AD). Studies from our group and others indicate that APP contributes to neurodegeneration in AD.

The project emphasizes sustainable practices in drug development, ensuring environmentally friendly manufacturing and responsible sourcing of materials. In terms of social value this product, it has been created since the begining to create an impact on the quality of life of both patients and their caregivers. Additionally, the project upholds ethical governance through transparency, diversity in research, and adherence to regulatory standards.

Our asset could have a high impact on therapeutic landscape of AD. This antibody could represent the first agent of a new set of therapies directed to treat APP dysregulation beyond amyloid plaques. This solution could be administered alone and/or in combination with anti-amyloid drugs, as second-line treatment for those patients who do not tolerate or respond to anti-amyloid drugs, or for certain subtypes of AD. In summary, our novel antibody represents a new therapeutic approach for AD and could enrich the therapeutic solutions for this devastating and prevalent disease.

The drugs currently approved for Alzheimer's disease (AD) in Europe are used exclusively to treat symptoms, but do not affect disease progression. In the last two years, the FDA has approved two new anti-amyloid drugs that slow disease progression. The proposed solution is a non-amyloid drug for Alzheimer's disease that targets a mechanism common to all AD subtypes. This novel therapeutic solution is based on a new monoclonal antibody that binds to the amyloid precursor protein (APP), thereby preventing the formation of Aβ plaques (the pathological hallmark of AD).

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The leading option currently under consideration is licensing the technology to an external industrial partner with the necessary infrastructure and regulatory experience to support advanced clinical development and commercialization. A licensing model that includes an upfront payment (covering, at minimum, patent-related expenses), milestone payments tied to regulatory and commercial development, and royalties on net sales.

Alzheimer's Disease (AD) affects 35 million people worldwide and it is expected that these numbers will triple by 2050 if an effective treatment is not found. In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care.

Relapsed/refractory patients with Alzheimer disease. Araclon/Grifols and Denali are potential partners due to the interest of the companies in AD therapeutics and immunotherapy. Araclon has an immunotherapy in AD in phase 2, and Denali is a small US-based biotech with different monoclonal antibodies in the pipeline for AD. Additionally, other medium and large companies involved in AD therapeutics are Eisai, Grifols, Biogen or Lilly, and the team has regular contact with them.

Funding for experimental part described in the application: 1) Study of the therapeutic effect of APP1B in cellular models; and 2) Study of the therapeutic effect of APP1B in animal models. Furthermore, funding for patent expenses and a market study to develop the business model are also sought.

Competitive funding for experimental part or co-development with industry (potential licensees)

The project has achieved its results thus far thanks to competitive funding awarded by the Instituto de Salud Carlos III (ISCIII) through grants PI20/01330, totalling €183,920 for the period 2021-2025, and PI23/01767, totalling €215,000 for the period 2024-2026. These two still active funds allowed the team to reach the TRL-3 and to identify the antibody APP1B.

A novel monoclonal antibody that binds to the intracellular fragment of APP, the precursor to the Aβ peptide.

In the U.S., two drugs are already on the market for the same indication: Lecanemab (Lequembi®) and Donanemab (Kisunla®). As the technology is developed, the product will need to navigate the entire european drugs regulatory process, with particular emphasis on assessing the drug's toxicology and clinical efficacy & safety.

Experimental Part: Study of the therapeutic effect of APP1B in cellular models (1S 2025) Study of the therapeutic effect of APP1B in animal models (2S 2025-1S 2026) Transfer activities: PCT submission (1S 2026)

Drafting of the PCT application

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TTO is certified with ISO 56001:2024 - Innovation management system by AENOR.

This novel therapy is being developed at the Institut de Recerca Sant Pau by a team led by Alberto Lleó, MD, PhD, Sònia Sirisi, PhD, and Érika Sánchez, with support from Carles Saura, PhD, and Arnaldo Parra, PhD, from the Universitat Autònoma de Barcelona. The research group aims to establish a spin-off company to license this therapy to pharmaceutical firms with the expertise for market-regulated preclinical and clinical trials. Our asset could have a high impact on therapeutic landscape of AD. This antibody could represent the first agent of a new set of therapies directed to treat APP dysregulation beyond amyloid plaques. This solution could be administered alone and/or in combination with anti-amyloid drugs, as second-line treatment for those patients who do not tolerate or respond to anti-amyloid drugs, or for certain subtypes of AD. In summary, our novel antibody represents a new therapeutic approach for AD and could enrich the therapeutic solutions for this devastating and prevalent disease.