Spain might be best known for its sunny beaches, tapas, and flamenco, among many other things, but in the last decade or so, its biotech industry has also quietly become an integral part of the country. The sector has grown dramatically, with international investors taking more of an interest in the country’s scientific landscape, turning it into one of the most competitive industries globally. In this article, we take a look at eight of the top biotech companies based in Spain today.
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Aelix Therapeutics
Aelix Therapeutics is a clinical-stage biotech company based in Barcelona, in the northeast of Spain. It is a spin-off of HIVACAT – a Catalan program for the development of therapeutic vaccines and prevention against human immunodeficiency virus (HIV) – and is focused on developing a new therapeutic vaccine for HIV that can be included in cure and eradication strategies.
The company’s vaccine program is based on an innovative T-cell vaccine immunogen design that directs the body’s immune defense to the most vulnerable parts of the HIV virus. The immunogen, called HTI, is based on the observation that T-cell responses to certain HIV regions are enriched in people with a non-progressor clinical phenotype. Therefore, HTI brings these beneficial regions together within a single vaccine.
AELIX-002, the first clinical trial run by the company, started in September 2017. It was a phase 1 trial that studied the HTI vaccine in early diagnosed, early treated HIV-infected individuals. The results showed that the vaccines were well tolerated, refocused killer T cells on more protective epitopes, and showed in a subgroup of participants that those who generated a stronger immune response were able to remain without antiretroviral treatment for longer periods of time and with a lower viral load compared to those who did not receive the vaccine or did not respond to the vaccination.
As part of an ongoing partnership with Gilead, Aelix announced positive topline results last year from its AELIX-003 trial, which evaluated the safety, tolerability, immunogenicity, and efficacy of the company’s vaccine in combination with Gilead’s investigational Toll-Like Receptor 7 (TLR7) agonist – vesatolimod (VES) – in people with HIV on antiretroviral therapy.
Highlight Therapeutics
Based in Valencia, Spain, the immuno-oncology biotech company Highlight Therapeutics is targeting anti-PD-1 resistance to try and transform cancer immunotherapy. Stimulation of the immune system using anti-PD-1 antibodies, also known as immune checkpoint inhibitors, significantly improves survival in cancers such as melanoma. However, these therapies are only effective in a subset of patients, leaving a significant portion unresponsive. Highlight believes its lead RNA-based drug candidate, BO-112, has a unique ability to modify tumor-intrinsic pathways and the immune system to make tumors more sensitive to immune checkpoint inhibitors. According to the company, the drug has been demonstrated to initiate a powerful immune response, leveraging a unique multi-target approach to turn ‘cold’ tumors ‘hot’, making them visible to the immune system.
BO-112 is currently being investigated in a range of clinical trials as a monotherapy and in combination with checkpoint inhibitors. It is currently being tested in combination with Merck & Co’s Keytruda. The two companies completed a successful phase 2 study to evaluate intra-tumoral administration of BO-112 and pembrolizumab in mucosal, acral, and cutaneous melanoma patients in August 2021.
The collaboration between Highlight and Merck is ongoing after Highlight signed a second phase 2 trial collaboration with Merck in 2020 to evaluate the BO-112 and Keytruda combination in patients that have progressed on anti-PD-1-based therapy in refractory advanced malignant melanoma.
Minoryx Therapeutics
Minoryx Therapeutics is focused on the discovery and development of novel therapies for severe, orphan genetic diseases of the central nervous system (CNS) with high unmet medical needs. The company’s lead candidate is a PPAR-γ agonist called leriglitazone. The drug has demonstrated brain penetration and a favorable safety profile and showed robust preclinical proof-of-concept in animal models of multiple diseases by modulating pathways leading to mitochondrial dysfunction, oxidative stress, neuroinflammation, demyelination, and axonal degeneration.
Leriglitazone is currently in late-stage trials to treat X-linked adrenoleukodystrophy (X-ALD), an orphan neurodegenerative disease caused by a mutation in the ABCD1 gene. X-ALD presents two main neurologic phenotypes, one of which is cerebral ALD (cALD), characterized by demyelinating brain lesions that may become rapidly progressive, leading to acute neurological decline and death. These lesions can produce severe symptoms such as loss of voluntary movements, inability to swallow, loss of communication, cortical blindness, and total incontinence, as well as death, with a mean survival of three to four years. In a phase 2/3 study, leriglitazone was found to significantly reduce the progression of cerebral lesions and reduce the incidence of progressive cALD in adult X-ALD patients. Last year, the U.S. Food and Drug Administration (FDA) also gave Minoryx the green light to begin a phase 3 trial of leriglitazone to treat X-ALD patients with cerebral adrenoleukodystrophy (cALD).
However, Minoryx announced in May that the EMA’s Committee for Medicinal Products for Human Use (CHMP) has recommended once again not to grant marketing authorization for leriglitazone as a treatment for cALD following the completion of a re-examination procedure. Minoryx’s chief executive officer (CEO) said in the press release update that the company will continue to generate evidence from two ongoing trials in order to get the drug approved.
Ona Therapeutics
A spin-off of the Catalan Institution for Research and Advanced Studies (ICREA) and the Barcelona Institute for Research in Biomedicine (IRB Barcelona), Ona Therapeutics specializes in the development of antibody drug conjugates (ADCs) to attack advanced cancer.
The company currently has its focus on two programs. Its lead candidate is ONA-255, which is an undisclosed first-in-class ADC that is being initially developed for a specific population of refractory breast cancer patients. The company is also developing a monoclonal antibody against CD36, a metabolic regulator of fatty acid transport that has been implicated in multiple aspects of cancer progression.
In 2020, Ona closed a €30 million ($33 million) series A funding round, which at the time, marked the largest round ever achieved by a biotech company in the preclinical stage in Spain.
More recently, in December 2023, the company entered into an agreement with Biocytogen Pharmaceuticals to develop ADCs targeting solid tumors. Under the terms of this agreement, Biocytogen grants Ona access to evaluate its proprietary RenMice-derived fully human antibodies against a specific tumor target, with an option to exclusively license selected antibodies for ADC development, manufacturing, and commercialization in mutually agreed indications and territories.
Oryzon Genomics
Oryzon Genomics is a public clinical-stage biopharmaceutical company focused on the development of innovative epigenetic personalized medicines for the treatment of neurological diseases and cancer.
Epigenetics is the study of how behavioral and environmental factors can cause changes in gene expression without changing an individual’s DNA sequence. Epigenetic switches also occur in normal biological or disease processes. Regulation of gene transcription and translation are key biological determinants for cellular differentiation and function, and transcriptional imbalances play a key role in several human diseases.
Oryzon’s therapeutic strategy is to target lysine-specific demethylase 1 (LSD1), which is a histone-modifying enzyme that is involved in the regulation of the expression of many genes that are important in the onset and progression of cancer and CNS disorders.
The company’s most advanced candidate is called vafidemstat, an oral small molecule that has been optimized for CNS indications and acts as a covalent inhibitor of LSD1. Although the drug recently failed to meet its primary endpoint of improving the symptoms of borderline personality disorder at weeks 8 to 12 as measured by the Borderline Personality Disorder Checklist – which measures instability, recurrent suicidal behavior, gestures, threats or self-mutilating behavior – in a phase 2b trial, it did meet its secondary endpoint of disorder severity across the same time span using a scale called Borderline Evaluation of Severity, and a statistically significant improvement in agitation and aggression was also seen. This has prompted Oryzon to move forward with vafidemstat, with plans to ask the FDA to take it into a phase 3 trial for borderline personality disorder, but with slightly different endpoints.
Peptomyc
Headquartered in Barcelona, Spain, biotech company Peptomyc is working on the development of a Myc inhibitor to treat cancer. Myc is a transcription factor that is expressed in over 70% of human cancers and is central to cancer proliferation, survival, and resistance to treatment.
Peptomycs candidate, OMO-103, is a miniprotein – commonly defined as being less than 100 amino acids long – that targets Myc. It consists of 91 amino acids, which have a unique ability to enter the cancer cell and penetrate its nucleus, meaning that it has the potential to overcome the challenges that small molecule therapeutics have previously encountered in targeting Myc – small molecules cannot recognize a protein that changes its shape all the time. OMO-103, on the other hand, is designed to chop Myc into a shape that cannot change; once Myc binds to OMO-103, it can no longer bind to DNA and therefore becomes inactive.
After a successful phase 1 study, in which 22 patients with various types of advanced tumors were enrolled, OMO-103 is now being tested in a phase 1b trial in combination with the standard-of-care regimen Gemcitabine and Nab-Paclitaxel in metastatic Pancreatic Ductal Adenocarcinoma (PDAC) – the most common form of pancreatic cancer – patients.
SpliceBio
SpliceBio’s initial focus is around developing a gene therapy for Stargardt disease, which is a rare genetic eye condition that occurs when fatty material builds up on the central part of the retina, called the macula. The disease primarily affects children and young adults, causing vision loss.
Stargardt disease is caused by an alteration in the ABCA4 gene. With its large size of 6.8kb, it is too large for single adeno-associated virus (AAV) vectors to package enough genetic material to treat it, so SpliceBio is focusing on harnessing the potential of inteins to overcome this limitation. Inteins are a family of proteins that carry out a process known as protein splicing, sticking peptides together to form new proteins, and the company’s co-founders were able to develop engineered split inteins for therapeutic use.
In 2022, SpliceBio raised €50 million ($52.7 million) in oversubscribed series A funding, which will go towards helping it take its lead program for Stargardt disease into phase 1 of clinical development.
Furthermore, in October 2023, the Spanish biotech company entered into a collaboration with Spark Therapeutics – a member of the Roche group – to develop a gene therapy for an undisclosed inherited retinal disease.
Tyris Therapeutics
Another biotech company based in Valencia, on the eastern coast of Spain, Tyris Therapeutics is working on the development of next-generation gene therapies for rare genetic diseases with both systemic and local delivery. The company has a DNA-based medicines platform that includes proprietary technology to produce linear closed DNA, just containing the sequence of interest, and novel non-viral vectors that do not trigger an immune response, have no limitation in cargo capacity, and enable re-administration of any gene therapy treatment. According to the company, this means that its platform can overcome current challenges in viral gene therapy, achieving more efficient and safer therapeutics for any genetic disease.
Tyris has a preclinical pipeline initially focused on dermatological indications, as well as on renal, hematological, and pulmonary indications. It is also exploring further applications for its technology platform to fuel innovation in more prevalent therapeutic approaches, such as vaccines, CAR-T therapies, or monoclonal antibodies (MABs).
In November 2021, Tyris entered into a strategic partnership with Almirall – a Barcelona-based pharmaceutical company focused on medical dermatology – to develop gene therapies for the treatment of debilitating genetic dermatological conditions.
The growing biotech scene in Spain
In 2019, the Spanish biotech sector invested over €940 million ($1.06 billion) in research and development (R&D), having doubled the number in the space of 10 years. And, in 2020, the total funding for biotechs in the country surpassed €150 million ($168.5 million). Furthermore, the country hosts BioSpain, one of the largest international biotech events in southern Europe, which attracts people from within the global biopharma industry. All of these factors are contributing to the growth of the biotech industry in the country. And with more and more biotech companies joining the scene in Spain, the industry will likely continue on its upward trajectory.