15 new therapies ‘made in Catalonia’

NÚRIA PELÁEZ 

A new company is launched every week in the BioRegion of Catalonia, the Catalan life sciences and health sector. Since 2008, investment in these start-ups has multiplied by 12, and the number of foreign investors in these emerging companies has risen from 0 to more than 50 in 10 years.

What are these resources used for? Bringing a new drug to market takes more than 10 years and costs more than €1 billion, and only 1 out of every 10,000 potential drugs ends up reaching patients. Currently, Catalan biomedical start-ups have almost 20 therapies in the clinical phase* (more information at the end of this post), a significant increase over the 7 that were in the pipeline in 2013. As a result of the sector’s development, Biocat estimates that some of these drugs may actually reach patients by around 2025. Let’s review these potential drugs in the most advanced phases which are currently being developed in the BioRegion of Catalonia:

VACCINES AND INFECTIOUS DISEASES

The Catalan HIV vaccine from AELIX Therapeutics

A vaccine that allows people infected with HIV to keep the virus under control by re-educating their own immune system: this is the goal of AELIX Therapeutics with its therapeutic vaccine based on the immunogen HTI. AELIX is a spin-off of the HIVACAT program led by IrsiCaixa and the Hospital Clínic with the support of partners like “la Caixa” and Esteve.

In 2016, AELIX closed the first round of funding with €11.5 million. In 2017, the company started its first phase Ib / IIa clinical trial, called AELIX-002: the final results will be available in late 2020. In October 2018, AELIX embarked on a partnership with Gilead Sciences to conduct another phase II study, called AELIX-003. In this study, the HTI vaccine is administered along with the Gilead drug vesatolimod. The results of this study are expected to be available in late 2021.

RUTI, the tuberculosis vaccine from Archivel Farma

Currently, there are around 15 potential vaccines against tuberculosis in the clinical phase around the world, the majority of which aim to prevent the disease. One of the few therapeutic vaccines to treat it is being developed in Catalonia, more specifically in Badalona: it is called RUTI and it is being developed by Archivel Farma.

The vaccine is being tested in a phase II clinical trial and the results are expected to be available in late 2020. Another phase II clinical trial will soon get underway to test the RUTI vaccine in patients with active tuberculosis and multi-drug-resistant tuberculosis. The vaccine’s capacity to activate a broad response in the immune system against different antigens has driven Archivel Farma to study its use for other conditions as well, such as to treat rhinitis and other allergic diseases, and immunotherapy for bladder cancer, an indication in which a phase I clinical trial is already underway (results expected in mid-2020). RUTI was designated an orphan drug by the European Medicines Agency in 2017.

ONCOLOGY

Autophagia, the promise of AbilityPharma in oncology

Ability Pharmaceuticals’ proposal for oncology is ABTL0812, a compound which causes the death of tumor cells by autophagia (self-digestion). The company has just closed a round of €3.5 million to complete phase II clinical studies in Europe in patients with endometrial cancer or squamous-cell lung cancer. In the United States, the FDA has already approved this same study (December 2017) and the protocol of another phase II study in pancreatic cancer. ABTL0812 was approved for an Orphan Drug Designation (ODD) for pancreatic cancer, bile duct cancer and pediatric neuroblastoma cancer by the FDA in the United States and the EMA in Europe.

Ever since it was founded in 2011 after splitting off from AB-Biotics, Ability Pharmaceuticals has raised more than €15 million. In 2016 the company signed an agreement with SciClone Pharmaceuticals to develop and commercialize the product in China, and it hopes to reach a licensing agreement with a global pharmaceutical company in order to continue to develop the drug and commercialize it in the future.

Hospital Clínic’s own CAR-T therapy

Three years ago, just like some university hospitals in the United States and China, the Hospital Clínic of Barcelona started preparing for its own academic CAR-T therapy. So far, the Hospital Clínic has treated the 35 patients required by the Spanish Medicines Agency (AEMPS) for its CAR-T therapy (called ARI1) to be used as a free treatment in patients with lymphoma and acute lymphoblastic leukemia in the National Health System. The Hospital Clínic expects it to be authorized in late 2019, and once approved, it can benefit a large number of patients at Spanish hospitals.

Unlike the CAR-T therapies of other pharmaceutical companies, the CAR-T therapy cells at the Hospital Clínic may not be sent to other countries. According to the Hospital Clínic, the cost of the therapy to the public system will be approximately one-third of the cost of pharmaceutical drugs.

VCN Biosciences: Viruses that attack tumors

Designing new treatments for cancer using oncolytic adenoviruses is the goal of VCN Biosciences, a company founded in 2009 by three researchers from the Institut Català d’Oncologia (ICO) and the Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). VCN Biosciences’ most advanced candidate is VCN-01, an adenovirus which is currently in the clinical development phase with patients who have different kinds of tumors (pancreatic cancer, retinoblastoma, head and neck tumors). The company is currently evaluating the combination of VCN-01 with immune checkpoint inhibitors: it has already started a first clinical trial in patients with metastatic squamous cell carcinoma of the head and neck and it plans to start more.

In 2012, 40% of its capital was acquired by Grifols. The company is currently raising a new round of funding and forging partnerships with pharma companies working in the field of immune checkpoint inhibitors.

ORY-1001, epigenetics of Oryzon in oncology

With a research center in Cornellà de Llobregat (Barcelona), Oryzon is the longest-standing biotech company in the BioRegion of Catalonia. The company, quoted on the Spanish stock market, develops new epigenetic therapies to treat oncological and neurodegenerative diseases using the enzyme LSD1 as the therapeutic target. The Oryzon pipeline currently includes three compounds, two of them in the clinical phase: iadademstat (also known as ORY-1001), an LSD1-selective inhibitor for cancer, and vafidemstat (also known as ORY-2001), an LSD1-optimised inhibitor for CNS for neurological diseases.

From 2014 to 2017, Oryzon was in a partnership with Roche, which led to revenues of more than 23 million dollars to develop iadademstat (ORY-1001), a small, orally administered molecule with a powerful differentiating effect in hematological and solid cancers, like small-cell lung cancer. Oryzon regained the rights to the drug and has made headway towards developing it with two phase II clinical studies underway: ALICE (acute myeloid leukemia)  and CLEPSIDRA (small-cell lung cancer). Just a few days ago, the company presented positive results on the efficacy of this latter study as part of the ESMO-2019 international conference in Barcelona. The final results of these studies are expected in the second half of 2020.

NEUROLOGY

The epigenetic candidate from Oryzon in neurology: ORY-2001

The Oryzon pipeline (see Oncology section above) currently includes an LSD1-optimised inhibitor for CNS for neurological diseases: vafidemstat (also known as ORY-2001).

Vafidemstat (ORY-2001) is a small, orally-administered molecule which acts on different levels to lower cognitive deterioration, memory loss and neuroinflammation, in addition to having neuroprotective effects. Oryzon has several phase II clinical studies underway with this molecule: the REIMAGINE and REIMAGINE-AD studies on aggressiveness in psychiatrically ill patients (autism spectrum syndrome, borderline personality disorder, attention deficit and hyperactivity disorder in adults) and Alzheimer’s patients, respectively; the ETHERAL and ETHERAL-US studies in patients with Alzheimer’s; and the SATEEN study on multiple sclerosis. The company plans to release the results of these studies starting in November 2019 and throughout 2020.

Bionure’s commitment to multiple sclerosis

Bionure was founded in 2009 as a spin-off of IDIBAPS and the CSIC. The company is currently focusing its efforts on multiple sclerosis and acute optic neuritis, a rare ophthalmologic disease for which BN201 is designated an orphan drug in Europe and the United States.

BN201 proved it can protect neurons and promote remyelination in model animals. Late 2017, the company welcome a first institutional VC investor, Alta Life Science, which led a Series A round to finance a first clinical phase 1 study that is already completed. Bionure recently closed an internal round and a second crowdfunding round to fund regulatory and technical preparations for the next phase 2 study in early 2020 to prove the efficacy of BN201 in patients who suffers from acute episodes of optic neuritis.

RARE DISEASES

Minoryx: 50 million to combat rare diseases

Finding innovative therapies for patients with rare diseases: this is the commitment of Minoryx, launched one of the biotech companies with the most meteoric rise in the BioRegion of Catalonia. The company has opened a branch in Belgium after closing one of the largest investment rounds in the sector: €21.3 million, led by the Belgian Fund+ in 2018. Since it was created, Minoryx has raised €50 million.

Its drug MIN-102 (leriglitazona) is currently in a phase II/III clinical trial to treat adrenomyeloneuropathy (AMN), the most common phenotype of X-linked adrenoleukodystrophy (X-ALD), a disease that affects one out of every 17,000 children born in the world. Minoryx’s drug is the most advanced drug to treat this disease currently in clinical development, and it has been categorized as an orphan drug to treat X-ALD in both Europe and the United States. The results of the study are expected in late 2020.

Minoryx is also ready to launch a second study with MIN-102 in X-ALD. This is a phase II study to treat cerebral X-ALD (CALD) in pediatric patients. MIN-102 is also in phase II to treat Friedreich’s ataxia (FRDA): results are expected at the end of 2020.

SOM Biotech: Accelerating cures for rare diseases

SOM Biotech, specialized in discovering and developing drugs to treat rare diseases, closed a round of €7 million in March 2019 in order to finish the phase IIa study of an innovative treatment for chorea associated with Huntington’s disease: the SOM3355 compound. The company expects this drug to reach the market within five years.

In 2016 SOM Biotech signed an exclusive global licensing agreement with the US company Corino Therapeutics Inc. for the clinical development and sale of the drug SOM0226 –showing very promising results in the phase IIa clinical study- to treat amyloid transthyretin amyloidosis (ATTR). In 2018 as well, SOM Biotech signed an exclusive global licensing agreement with U-Cell Therapeutics Inc. (Singapore) for the SOM0777 compound to treat brain cancer.

SOM Biotech has an extensive product portfolio which includes projects about to enter phase IIa (SOM1201, Adrenoleukodystrophy), and other compounds in preclinical phases.

CARDIOVASCULAR AND BLOOD

The vasculoprotective drug against stroke from FreeOx Biotech

Stroke, one of the leading causes of death and disability around the world, is the main target of FreeOx Biotech, a young biotech company founded in 2017 by five entrepreneurs from Barcelona and Pittsburgh as a spin-out of Hospital Clínic de Barcelona-IDIBAPS. The company has two molecules to treat stroke and other diseases of the central nervous system: Ox-01 and Ox-02.

The more advanced one, Ox-01, has a proven preventative effect against the damage caused by the reperfusion after stroke and has concluded its phase IIb clinical trial. In November 2018, the company concluded its first round of €500,000 with private investors in order to prepare to embark on clinical phase III of Ox-01 in 2020 and conduct pre-clinical studies with Ox-02. The company is seeking investors and/or licensees for a Series B round to complete the clinical development of Ox-01 and secure its commercial authorization in the leading global markets.

The antihemorrhagic agent in phase III from Thrombotargets

Thrombotargets has one of the most advanced therapies in development in the BioRegion of Catalonia, TT-173, currently in phase III. It is a topical, lyophilized antihemorrhagic agent which drastically lowers the bleeding time of a surgical hemorrhage. TT-173 has already successfully passed a phase I clinical trial in dental extraction and a phase II clinical trial in skin grafting, and it currently has a phase II/III study underway in total knee arthroplasty, the results of which are expected in 2020. Once the current phase II/III clinical trial is completed, the company will undertake a phase III in liver surgery to complete the drug registration with the European Medicines Agency (EMA) and the FDA in the United States.

Thrombotargets is headquartered in Castelldefels (Barcelona), where it conducts part of its R&D. The company is currently in a capitalization phase for €12 million. Ever since it was created, Thrombotargets has raised a total of €29 million.

If you want to know more about these therapies, download an extended version of this post here.

*A clinical trial is an experimental study that aims to obtain information on how effective and safe a drug, treatment or medical device is for human use.

We break clinical trials down into phase I, II, III and IV depending on how close a drug is to market.

Phase I serves to show that a new treatment is safe for human use. Phase I trials are normally done on small groups of people (often healthy volunteers) and indicate the right dosage for continued research.

Phase II serves to obtain more information on the safety of the new treatment and demonstrate how effective it is at treating a specific condition. In this phase, the proper therapeutic dose is also established.

Phase III serves to compare the new drug with the standard available treatment. Phase III trials are normally done on a large group of people and, if they show results that are beneficial to patients, the drug gets permission to be marketed.

Phase IV serves to research the effectiveness of a drug for the general population and collect more data regarding safety and quality of life. These trials are done after a drug is available on the market.