Nuage Therapeutics, based at the Barcelona Science Park (PCB-UB), has secured €2.7 million in funding from the Spanish State Research Agency (AEI) of the Ministry of Science, Innovation and Universities under the R&D&I State Program for Transfer and Collaboration. The funding will support a 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), the European Molecular Biology Laboratory in Barcelona (EMBL Barcelona), and the Vall d’Hebron Institute of Oncology (VHIO). The main objective of the project is to reach the clinical phase with a robust dataset demonstrating the efficacy and safety of the drug candidate NTX-A, which has been one of the primary focus of resources over the past year. 

This grant validates our approach to tackling intrinsically disordered proteins and accelerates our mission to deliver a new generation of transformative precision therapies for severe illnesses where effective treatments are still lacking”

– Stuart Hughes, CEO Nuage Therapeutics

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.  

“This grant validates our approach to tackling intrinsically disordered proteins and accelerates our mission to deliver a new generation of transformative precision therapies for severe illnesses where effective treatments are still lacking” says Stuart Hughes, recently appointed CEO of Nuage Therapeutics. 

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

“We are very excited to be a key partner in this project and bring the expertise of 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.” Talya Dayton, Group Leader at EMBL Barcelona. Dayton and her group will lead the development of advanced laboratory models, called patient derived tumour organoids (PDTOs), that are grown directly from patients’ 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 against cell survival, gene activity, ASCL1 expression, and toxicity, helping the team identify the most effective and safest candidates for future preclinical development. 

“The 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”, indicates Dr. Marcos Malumbres, Director of the Systems Oncology programme and head of the Cancer Cell Cycle laboratory at VHIO. “However, 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.” 

Innovation for “undruggable” proteins

A large proportion of the human proteome contains proteins with high levels of intrinsic structural disorder and, therefore, are not suitable for conventional drug discovery methods. Around 40% of human proteins include intrinsically disordered regions (IDRs). These regions — and, in some cases, entire proteins — 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 participate in a wide range of cellular processes, but it also makes them elusive targets for traditional drugs. 

In cancer, this property is particularly relevant, as many proteins involved in tumour onset and progression — such as oncogenic transcription factors — 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. 

Nuage Therapeutics has developed an innovative technology that enables interrogating intrinsically disordered proteins (IDPs) in their transient more ordered structures, in which they are susceptible to being recognized and inhibited by drugs. This strategy opens up a new avenue for designing therapies against proteins that, until now, were considered undruggable. 

The company’s patented platform enables to zoom in on the temporarily adopted IDP structures, which are relevant in the native cellular context. This allows researchers to design drugs capable of recognizing and acting on them—something that was previously impossible. This breakthrough represents a paradigm shift in 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. 

A new strategy against the most aggressive form of lung cancer

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. 

In cancer, many proteins involved in tumour initiation and progression — such as oncogenic transcription factors — 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. 

In this context, Nuage Therapeutics is opening a new path to tackle small-cell lung cancer of the SCLC-A subtype, a form responsible for a significant proportion of SCLC cases and one that currently lacks effective treatments. By allowing to interrogate the ASCL1 protein’s transiently adopted stable structures, this technology could allow the identification of molecules that bind to it and neutralize its oncogenic activity. 

Beyond this tumour, Nuage Therapeutics’ breakthrough could extend to other diseases driven by disordered proteins, establishing a new frontier in the rational development of drugs. 

Funding Acknowledgement

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.  

Research Project Reference: CPP2024-011304. Funded by MICIU/AEI. 

Nuage Therapeutics has successfully completed two projects funded through the Torres Quevedo programme (PTQ2021-011961 & PTQ2021-011994), strengthening its pioneering role in drug discovery.

These projects have supported Nuage’s development of a novel drug discovery approach, unlocking the draggability of intrinsically disordered proteins (IDPs) to deliver a new wave of transformative therapies. IDPs are a class of proteins long considered undraggable. This breakthrough opens the door to a new generation of transformative therapies.

This ground-breaking approach is currently being applied to target transcription factors that drive the growth of specific cancers, offering a revolutionary approach to treating certain tumour types.

Scientific, economic & strategic impact

The execution of these projects has had a transformative impact on Nuage’s trajectory as it has achieved several outstanding milestones:

Funding acknowledgement

The Torres Quevedo Programme is awarded by the Spanish State Research Agency (AEI) under the Spanish State Plan for Scientific, Technical and Innovation Research 2021-2023. 

Ayuda PTQ2021-011961 y PTQ2021-011994 financiada por MICIU/AEI/10.13039/501100011033 (Ministerio de Ciencia, Innovación y Universidades / Agencia Estatal de Investigación)

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Nuage Therapeutics has been awarded a €352,874 Eurostars grant to accelerate the development of NT-A, a first-in-class covalent therapeutic candidate for the treatment of ASCL1-driven small cell lung cancer (SCLC-A). The project, entitled “Unlocking druggability of disordered proteins: NT-A, a first-in-class therapeutic for small cell lung cancer, and novel platforms to support the development of covalent drugs for disordered targets”, will run from April 1, 2025, to March 31, 2027. 

Eurostars is a European research funding programme designed to support innovative small and medium-sized enterprises (SMEs). This funding will enable Nuage Tx to advance one of its most disruptive research areas: the development of therapies targeting Intrinsically Disordered Proteins (IDPs), a class of proteins that has historically been considered inaccessible to conventional drug discovery approaches. 

The main objectives of the project are: 

This new funding will enable Nuage Tx to advance key translational components of the program, including the establishment of a robust PK/PD framework for covalent IDP‑targeting molecules, the development and deployment of next‑generation chemoproteomic approaches to assess target engagement in biological systems, and the exploration of novel mechanisms that may enhance selectivity and safety.  

The Eurostars grant will enable Nuage Tx to continue demonstrating that its novel technology can unlock the druggability of Intrinsically Disordered Proteins (IDPs), a class of proteins long considered “undraggable”. IDPs play a critical role in multiple diseases across different therapeutic areas, including oncology. Nuage’s proprietary technology makes these disordered proteins, which lack a stable shape, temporarily adopt a defined structure. As a result, researchers can design drugs capable of recognising and acting on them, something that was previously impossible. This breakthrough represents a significant shift in drug discovery, turning protein “disorder” into a therapeutic opportunity.   

Nuage’s groundbreaking approach is initially being deployed to target transcription factors that are key to the growth of specific cancers. With this new funding, Nuage Tx will continue advancing its innovative research, targeting oncogenic transcription factors that drive cancer progression while shutting down key disease pathways that have remained inaccessible to conventional drug discovery.   

Funding Acknowledgment

Funded by CDTI. This project has been supported by the Spanish Ministry of Science, Innovation and Universities. 

This project has received funding from the Eurostars-3 Programme, co-funded by CDTI and the European Union’s Horizon Europe Research and Innovation Framework Programme. 

Nuage Tx recibe una subvención Eurostars para desarrollar un inhibidor covalente pionero dirige al cáncer de pulmón microcítico impulsado por ASCL1 (SCLC-A)

Nuage Therapeutics ha sido seleccionada para recibir una subvención Eurostars de €352.874 para acelerar el desarrollo de NT-A, un candidato terapéutico covalente primero en su clase dirigido al tratamiento del cáncer de pulmón microcítico impulsado por ASCL1 (SCLC-A). El proyecto, titulado “Unlocking druggability of disordered proteins: NT-A, a first-in-class therapeutic for small cell lung cancer, and novel platforms to support the development of covalent drugs for disordered targets”, se desarrollará entre el 1 de abril de 2025 y el 31 de marzo de 2027. 

Eurostars es un programa europeo de financiación de la investigación dirigido a pequeñas y medianas empresas (pymes) innovadoras. La ayuda permitirá a Nuage Tx avanzar en una de sus áreas de investigación más disruptivas: el desarrollo de terapias dirigidas frente a proteínas intrínsecamente desordenadas (IDPs), una clase de proteínas que históricamente se ha considerado inaccesible para el desarrollo farmacológico convencional. 

Los principales objetivos del proyecto son: 

Esta nueva financiación permitirá a Nuage Tx avanzar en componentes translaciónales clave del programa, incluyendo el establecimiento de un sólido marco farmacocinético/farmacodinámico (PK/PD) para moléculas covalentes dirigidas a proteínas intrínsecamente desordenadas (IDPs), el desarrollo e implementación de enfoques quimioproteómicos de nueva generación para evaluar la interacción con la diana terapéutica en sistemas biológicos, y la exploración de nuevos mecanismos que puedan mejorar la selectividad y la seguridad de estos compuestos.

La subvención Eurostars permitirá a Nuage Tx seguir demostrando que su novedosa tecnología puede hacer accesibles al desarrollo farmacológico las proteínas intrínsecamente desordenadas (IDPs), una clase de proteínas que durante mucho tiempo se ha considerado “no farmacológicamente abordable” (undruggable). Las IDPs desempeñan un papel fundamental en múltiples enfermedades de distintas áreas terapéuticas, incluida la oncología. 

La tecnología propietaria de Nuage permite que estas proteínas desordenadas, que carecen de una estructura estable, adopten temporalmente una conformación definida. Gracias a ello, los investigadores pueden diseñar fármacos capaces de reconocerlas y actuar sobre ellas, algo que anteriormente era imposible. Este avance representa un cambio significativo en el descubrimiento de fármacos, al convertir el “desorden” proteico en una oportunidad terapéutica.

El enfoque innovador de Nuage se está aplicando inicialmente al desarrollo de terapias dirigidas contra factores de transcripción clave para el desarrollo de determinados tipos de cáncer. Con esta nueva financiación, Nuage Tx continuará impulsando su investigación pionera para abordar factores de transcripción oncogénicos que impulsan la progresión tumoral, bloqueando vías esenciales de la enfermedad que hasta ahora habían permanecido fuera del alcance de las estrategias convencionales de descubrimiento de fármacos.

Financiación

Subvencionado por el CDTI. Este proyecto ha sido apoyado por el Ministerio de Ciencia, Innovación y Universidades. 

Este proyecto ha recibido financiación del Programa Eurostars-3 con cofinanciación de CDTI y del Programa Marco de Investigación e Innovación «Horizonte Europa» de la Unión Europea