{"id":77715,"date":"2025-12-09T11:29:30","date_gmt":"2025-12-09T10:29:30","guid":{"rendered":"https:\/\/www.embl.org\/news\/?post_type=awards&p=77715"},"modified":"2025-12-09T11:29:30","modified_gmt":"2025-12-09T10:29:30","slug":"nuage-therapeutics-obtains-e2-7-million-to-develop-a-pioneering-treatment-against-the-most-aggressive-lung-cancer","status":"publish","type":"awards","link":"https:\/\/www.embl.org\/news\/awards-honours\/nuage-therapeutics-obtains-e2-7-million-to-develop-a-pioneering-treatment-against-the-most-aggressive-lung-cancer","title":{"rendered":"Nuage Therapeutics obtains \u20ac2.7 million to develop a pioneering treatment against the most aggressive lung cancer"},"content":{"rendered":"\n

Joint press release with Nuage Therapeutics<\/em><\/p>\n\n\n\n

Nuage Therapeutics has secured\u00a0\u20ac2.7 million in funding from the Spanish State Research Agency (AEI)\u00a0<\/strong>of the Ministry of Science, Innovation and Universities under the R&D&I\u00a0State Programme for Transfer and Collaboration. The funding will support\u00a0a research project focused on developing a new drug against the most common subtype of small-cell lung cancer (SCLC-A), in collaboration with the Spanish National Cancer Research Centre (CNIO<\/a>), the European Molecular Biology Laboratory in Barcelona (EMBL Barcelona<\/a>), and the Vall\u00a0d\u2019Hebron\u00a0Institute of Oncology (VHIO<\/a>). The main\u00a0objective\u00a0of the project is to reach the clinical phase with a robust dataset\u00a0demonstrating\u00a0the efficacy and safety of\u00a0the\u00a0drug candidate\u00a0NTX-A, which has been\u00a0one of\u00a0the primary focus of resources over the past year.\u00a0<\/p>\n\n\n\n

The consortium has already initiated the development of NTX-A, a pioneering drug targeting the ASCL1 protein, which plays a key role in the onset of the most common type of small-cell lung cancer (SCLC-A). This subtype is associated with a pronounced neuroendocrine profile and rapid tumour progression, contributing to its particularly aggressive clinical behaviour.  <\/p>\n\n\n\n

\u201cThis grant validates our approach to tackling intrinsically disordered proteins and accelerates our mission to\u00a0deliver\u00a0a new generation of transformative precision therapies for\u00a0severe illnesses where effective treatments are still lacking,\u201d says\u00a0Stuart Hughes,\u00a0recently appointed CEO<\/a>\u00a0of\u00a0Nuage\u00a0Therapeutics.\u00a0<\/p>\n\n\n\n

The spin-off from the Institute for Research in Biomedicine (IRB Barcelona) is dedicated to pioneering a novel drug discovery approach, directly targeting <\/strong>intrinsically disordered proteins (IDPs) \u2014 therapeutic targets traditionally considered undruggable and associated with serious diseases such as cancer, which have so far remained beyond the reach of conventional treatments. <\/p>\n\n\n\n

\u201cWe are\u00a0very excited\u00a0to be a key partner in this project and bring the\u00a0expertise\u00a0of organoid development that we have at EMBL Barcelona. It is through interdisciplinary partnerships like this one that we can effectively advance in the field of cancer research,\u201d\u00a0says Dr. Talya Dayton,\u00a0Group Leader at\u00a0EMBL Barcelona<\/strong><\/a>.\u00a0Dayton and her group will lead the development of advanced laboratory models, called patient derived tumour organoids (PDTOs), that are grown directly from patients\u2019 tumour tissue to closely mimic real tumours. Once developed, the organoids will be classified by their molecular subtypes and ASCL1 status to test protein inhibitors and their ability to stop tumour growth. The effects of the drugs will be assessed\u00a0against\u00a0cell survival, gene activity, ASCL1 expression, and toxicity, helping the team\u00a0identify\u00a0the most effective and safest candidates for future preclinical development.\u00a0<\/p>\n\n\n\n

\u201cThe main goal of the project is to inhibit ASCL1, a protein that not only gives the name to a subtype of small cell lung cancer, SCLC-A, but is also known to drive this disease,\u201d indicates\u00a0Dr. Marcos\u00a0Malumbres, Director of the Systems Oncology programme and head of the\u00a0Cancer Cell Cycle laboratory at\u00a0VHIO<\/strong><\/a>. \u201cHowever, we also know that aggressive tumours evolve, especially under some therapies, and may lose their dependence on ASCL1. We will investigate these mechanisms of tumour evolution and resistance to ASCL1 inhibitors for a better future application of this type of therapies in the clinic.\u201d\u00a0<\/p>\n\n\n\n

Innovation for ‘undruggable’ proteins<\/h2>\n\n\n\n

A large proportion\u00a0of the human proteome\u00a0contains\u00a0proteins with\u00a0high levels\u00a0of intrinsic structural disorder and, therefore, are not suitable for conventional drug discovery methods.\u00a0Around 40% of human proteins include intrinsically disordered regions\u00a0(IDRs). These regions \u2014 and, in some cases, entire proteins \u2014 do not adopt a fixed and stable three-dimensional structure but instead remain flexible and dynamic, like ‘molecular chains’ in constant motion. This flexibility allows them to interact with many other molecules and\u00a0participate\u00a0in a wide range of cellular processes, but it also makes them\u00a0elusive targets for traditional drugs.\u00a0<\/p>\n\n\n\n

In cancer, this property is particularly relevant, as many proteins involved in tumour onset and progression \u2014 such as oncogenic transcription factors \u2014 exhibit a high degree of structural disorder. These proteins regulate the activity of numerous genes and control processes such as cell division and differentiation, but their flexible nature keeps them beyond the reach of classical therapeutic approaches, representing one of the major challenges in modern biomedicine. <\/p>\n\n\n\n

Nuage\u00a0Therapeutics has developed\u00a0an innovative technology that enables\u00a0interrogating\u00a0intrinsically disordered proteins (IDPs)\u00a0in their\u00a0transient more ordered structures,\u00a0in which they are susceptible to being recognised and inhibited by drugs. This strategy\u00a0opens up\u00a0a new avenue for designing therapies against proteins that, until now, were considered undruggable.\u00a0<\/p>\n\n\n\n

The company\u2019s patented platform enables to\u00a0zoom in on the\u00a0temporarily adopted\u00a0IDP\u00a0structures, which are relevant in the native cellular context. This allows researchers to design drugs capable of recognising and acting on them \u2014 something that was previously impossible.\u00a0This breakthrough\u00a0represents\u00a0a paradigm shift\u00a0in drug discovery, turning protein ‘disorder’ into a therapeutic opportunity. For years, these proteins were considered unreachable targets due to their flexibility and the difficulty of controlling their function with traditional compounds.\u00a0<\/p>\n\n\n\n

A new strategy against the most aggressive form of lung cancer<\/h2>\n\n\n\n

Among the diseases that could benefit from this technology, small-cell lung cancer (SCLC) stands out as one of the most aggressive and difficult-to-treat forms. Despite advances in immunotherapy and chemotherapy, treatment options remain limited, and patient survival has barely improved in recent decades. <\/p>\n\n\n\n

In cancer, many proteins involved in tumour initiation and progression \u2014 such as oncogenic transcription factors \u2014 exhibit a high degree of structural disorder. These proteins regulate the activity of numerous genes and control processes such as cell division and differentiation, but their flexible nature keeps them beyond the reach of classical therapeutic approaches, representing one of the major challenges in modern biomedicine. In this type of lung tumour, the ASCL1 protein drives the growth and survival of cancer cells by reactivating neural development genes that, when out of control, fuel the spread of the disease. <\/p>\n\n\n\n

In this context,\u00a0Nuage\u00a0Therapeutics is opening a new path to tackle small-cell lung cancer of the SCLC-A subtype,\u00a0a form responsible for\u00a0a significant proportion\u00a0of SCLC cases and one that currently lacks effective treatments.\u00a0By allowing to interrogate\u00a0the ASCL1\u00a0protein\u2019s\u00a0transiently adopted\u00a0stable structures,\u00a0this technology could\u00a0allow the identification of molecules that bind to it and neutralise its oncogenic activity.\u00a0<\/p>\n\n\n\n

Beyond this tumour, Nuage Therapeutics\u2019 breakthrough could extend to other diseases driven by disordered proteins, establishing a new frontier in the rational development of drugs. <\/p>\n\n\n\n

Funding Acknowledgement<\/h3>\n\n\n\n

The Public-Private Partnership Programme is awarded by the Spanish State Research Agency (AEI) under the Spanish State Plan for Scientific, Technical and Innovation Research 2024-2027.  <\/p>\n\n\n\n

Research Project Reference: CPP2024-011304. Funded by MICIU\/AEI.<\/em> <\/p>\n","protected":false},"excerpt":{"rendered":"

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