The Spanish company combines pharmaceutical research and development with business capabilities to translate scientific knowledge into new therapeutic opportunities.
AP-2, its most advanced program, currently in Phase I, is investigating a new approach to targeting TDP-43 protein dysfunction associated with ALS, with the aim of reversing or curing the disease.
Dr. Ana Martínez and Dr. Carmen Gil, co-founders of Molefy Pharma and researchers at the Margarita Salas Center for Biological Research (CIB-CSIC), explained the scientific origins and development of its therapeutic candidate AP-2.
Madrid, September 16, 2026. – Molefy Pharma, a Spanish company that evolved from a spin-off of the Spanish National Research Council (CSIC) and is backed by the ARQUIMEA Group, has presented its scientific and business project aimed at advancing the research and development of new therapies for neurodegenerative diseases.
The Spanish biotechnology company outlined its strategy for transforming scientific knowledge generated at CSIC into new therapeutic candidates for neurodegenerative diseases. To achieve this, it combines research in medicinal chemistry and neurobiology with preclinical development, pharmaceutical manufacturing, and clinical development capabilities, with the aim of advancing molecules targeting mechanisms involved in neuronal degeneration.
The presentation featured Alfonso de Egaña, General Manager of Molefy Pharma; Dr. Ana Martínez, co-founder of the company and principal investigator of the study; and Dr. Carmen Gil, co-founder of the company and principal investigator of the study.
“The company was created with the aim of researching therapeutic advances that can bring hope to patients with neurodegenerative diseases. That is why we focus on investigating new molecules that could help find a cure for neurodegenerative diseases such as ALS,” explained Dr. Ana Martínez.
From Public Research to the Development of New Medicines
Molefy Pharma structures its strategy around biological mechanisms shared by different neurodegenerative diseases. TDP-43 dysfunction is observed in virtually all cases of ALS, is one of the main pathological hallmarks of certain forms of frontotemporal dementia, and has also been identified in other neurodegenerative processes.
This approach makes it possible to investigate small molecules capable of acting on shared cellular processes, rather than addressing each disease exclusively as an independent condition. AP-2, whose first clinical indication is ALS, represents the first application of this strategy.
Founded in 2024, Molefy Pharma brings together a team with experience in biomedical research, pharmaceutical development, and business management, and has an independent Scientific Advisory Board that evaluates the scientific rationale and robustness of its programs. This combination brings different scientific and strategic perspectives into decision-making and helps keep its research aligned with developments in the sector and new opportunities for collaboration.
“Molefy Pharma was created to build a bridge between scientific research and the development of new medicines. We have the knowledge required to achieve this, together with ARQUIMEA’s technological, industrial, and business capabilities to drive these programs forward,” said Alfonso de Egaña, General Manager of Molefy Pharma. “Our commitment is to develop each program rigorously, without creating premature expectations, but with the ambition to provide new answers for diseases that still have very limited treatment options today.”
AP-2, New Hope in ALS Research
AP-2 is Molefy Pharma’s most advanced therapeutic candidate and the first of the company’s programs to enter clinical evaluation. It is an orally administered small molecule designed to target TDP-43 dysfunction, a protein that plays a key role in cellular function and whose dysfunction is closely associated with amyotrophic lateral sclerosis (ALS).
However, the relevance of TDP-43 extends beyond ALS, as alterations in this protein are also involved in different neurodegenerative processes. For this reason, understanding the mechanisms that alter its localization and function has become an important area of research in the search for new therapeutic strategies for neurodegenerative diseases.
Under normal conditions, TDP-43 is primarily located in the cell nucleus, where it is involved in RNA processing. In ALS, however, it can undergo abnormal phosphorylation, leave the nucleus, and accumulate in the cytosol. This alteration affects its normal function and can lead to defective cellular messages and reduced production of proteins required for motor neuron communication and survival.
The research that led to AP-2 investigated the inhibition of the CK1δ kinase as a strategy to reduce pathological TDP-43 phosphorylation. In patient-derived cellular models and animal models, the molecule under investigation showed reduced phosphorylation, restoration of TDP-43 localization, and preservation of motor neurons.
“In preclinical models, AP-2 has helped restore the normal localization and function of TDP-43 and has shown increased motor neuron survival in animal models,” said Dr. Carmen Gil. “These results support a strategy aimed at targeting one of the mechanisms associated with ALS progression, rather than focusing solely on its consequences. Clinical development will now determine whether these effects can be translated to humans,” she added.
AP-2 is currently being evaluated in a Phase Ia clinical trial in healthy volunteers, designed to characterize its safety, tolerability, and pharmacokinetic profile in humans. Although the study is still ongoing, data obtained to date show a favorable profile that supports the continued progression of the clinical program. This first phase is expected to be completed in early 2027, followed by a Phase Ib study in a small group of ALS patients, which will provide preliminary information on its safety and pharmacokinetics in patients.