A Second Look at Signia, an Early EIC Accelerator Antiviral Winner

Signia Therapeutics set out to find antivirals among medicines that are already on pharmacy shelves. The Lyon company, a spin-off of the VirPath virology laboratory, compared the gene-expression "signature" of cells infected by a respiratory virus with the signatures that thousands of approved drugs leave on cells, and looked for drugs that pushed infected cells back towards health. Its best-known find was diltiazem, a calcium channel blocker prescribed for heart conditions. In the European Commission's list of winners of the 8 January 2020 EIC Accelerator pilot cut-off, Signia appears as a grant-only winner from Villeurbanne, on its own with no partner company. CORDIS records an EU contribution of €2,382,284.45 towards a €3,403,263.50 project.

The project promised to finish the drug-matching platform and to take nebulised diltiazem into clinical validation against influenza. The platform work was reported as done. No trial of nebulised diltiazem was ever registered, a hospital trial of oral diltiazem that Signia backed was withdrawn before it enrolled anyone, and in October 2023, five months after the EIC project ended, the Lyon commercial court placed the company in judicial liquidation, according to the official insolvency notices in BODACC and the company record on societe.com.

What Is Left of Signia Therapeutics

Nothing operates under the Signia name any more. The French company register, through the government's company search service behind annuaire-entreprises.data.gouv.fr, lists Signia Therapeutics as closed with effect from 22 May 2024. The BODACC notices give the sequence: the Lyon commercial court opened a judicial liquidation (liquidation judiciaire) on 26 October 2023, fixed the date on which the company stopped paying its debts at 1 October 2023, and appointed the Lyon firm Selarl Marie Dubois as liquidator. The statement of creditors' claims was filed in March 2024, and on 22 May 2024 the court closed the liquidation "pour insuffisance d'actif", for insufficient assets. Societe.com records the same dates and the deregistration.

Its web address went with it. On 9 October 2026, www.signiatherapeutics.com served an Indonesian online gambling page instead of the company's site. The Internet Archive was offline when this article was researched, so earlier versions of the site could not be checked.

The Technology: Reversing the Infected Cell's Signature

Most antivirals hit a part of the virus itself, such as the enzyme that copies its genome. That works until the virus mutates, and each drug covers few viruses. Signia's founders turned the question around. Instead of targeting the virus, they targeted the infected cell: they recorded which genes a virus switches on and off in human airway cells, then searched a database of drug signatures for compounds that do the opposite. CORDIS describes the approach as "targeting the global response of the host cell instead of a specific molecular determinant of the pathogen", which in theory gives broad-spectrum drugs and makes resistance harder.

Because the candidates are approved drugs or shelved pharma compounds, their safety is largely known, which is the case for repurposing: shorter, cheaper development. The 2018 Phase 1 feasibility project, a €50,000 SME Instrument grant, put it as drug discovery that "becomes faster, safer and cost-efficient". The catch, common to all repurposing, is that a known drug still has to win a trial in the new disease, and the patent position on an off-patent molecule is weaker than for a new one.

The method came out of public research. A 2019 paper in Frontiers in Immunology by the VirPath team, with Andrés Pizzorno as first author and Manuel Rosa-Calatrava as senior author, showed that diltiazem cut influenza replication in reconstituted human airway tissue and improved survival in infected mice. Its competing-interests statement says the patent application on diltiazem and etilefrine as anti-influenza agents was filed by Inserm, Université Claude Bernard Lyon 1, Laval University and Hospices Civils de Lyon, not by Signia. What rights Signia held to that patent is not public.

Diltiazem's Two Trials That Did Not Deliver

Diltiazem had already been tested in people before the EIC award, but not by Signia. FLUNEXT, a Phase II trial of diltiazem plus oseltamivir (Tamiflu) in patients in intensive care with severe influenza A, began in January 2018 (the registry gives 23 December 2017) and aimed to enrol 300 patients in ten units, according to an Inserm press note, which says the results of the strategy "have led to the creation of a startup called Signia Therapeutics". The sponsor was Lille University Hospital. ClinicalTrials.gov lists the trial as terminated on 4 May 2022 after 85 patients, giving the reason as the "rate of inclusion and study affected by covid-19 epidemic", and no results have been posted there. The EU Clinical Trials Register also records it as prematurely ended.

The second trial was Signia's own bet. In October 2021 the listed French biotech Néovacs invested €1.3 million in Signia, "notamment" to fund the start of a Phase IIb trial of diltiazem in hospitalised COVID-19 patients with the Hospices Civils de Lyon, according to Néovacs' announcement. The trial, DICOV, was registered on ClinicalTrials.gov with the Hospices Civils de Lyon as sponsor and Signia Therapeutics as collaborator. It is listed as withdrawn, meaning no patient was enrolled, because "the epidemiological situation has changed considerably"; the entry was last updated on 26 May 2023, five days before the EIC project ended.

What the EIC Project Promised, and What CORDIS Shows

The grant agreement was signed on 14 May 2020 and the project ran from 1 June 2020 to 31 May 2023, on schedule, under the SME Instrument topic that the 2020 EIC Accelerator pilot used. Its objective was to develop "the full capability of the platform" and to "proceed with the clinical validation" of optimised nebulised diltiazem. The project's published report covers the platform work in detail and does not mention a clinical trial.

1. Upgrade the signature data bank and AI screeningDeliveredCORDIS reports a new computational architecture, AI-based algorithms and 500 new compound signatures.
2. In silico screening against respiratory virusesDelivered"30 drug candidates" against SARS-CoV-2, influenza and/or RSV, per the CORDIS report.
3. Preclinical validation of candidatesPartlyOne oral candidate validated against SARS-CoV-2 and "promising results" on four viruses; the candidates are not named.
4. Clinical validation of nebulised diltiazem for influenzaNot achievedNo trial registered; the oral COVID-19 trial Signia backed was withdrawn.
5. A company able to take candidates to marketNot achievedLiquidated in October 2023; no licence or pharma partnership announced.

The platform half of the project left a public trace in research papers. Signia staff are co-authors of a 2020 study in Cell Reports Medicine, which found that adding diltiazem lowered the dose of remdesivir needed against SARS-CoV-2 in human airway tissue, and of a 2024 benchmarking method for signature matching in Briefings in Bioinformatics, which credits the EIC Accelerator grant 954353 as funding. A 2025 paper in Antiviral Research, listed on Europe PMC with three authors affiliated with Signia, reported that diltiazem boosted baloxavir against influenza and molnupiravir against SARS-CoV-2 in the laboratory. It appeared after the company had closed.

The Money Around the Grant

Signia's other funding is documented mainly by its backers. Néovacs said it invested €1.3 million in October 2021, and its 2021 annual results release repeats the figure. On 5 January 2022 Signia announced a €1.7 million Deeptech development aid from Bpifrance for a €3.7 million, 36-month programme to scale up its platform, now called SIGNATURA, in a press release that also said it was raising a €16 million Series A with a first tranche of €4 million, and that it aimed to move several candidates towards the clinic by the end of 2022. The Bpifrance figure is also listed by tech.eu and Life Sciences Europe. No closing of the Series A could be found.

The BODACC notices record share capital changes in January and April 2022 and again in September 2023, a month before the company stopped paying its debts; the amounts are not in the notices. Signia filed its accounts for 2018 to 2022 with a confidentiality declaration, so revenue, losses and staff numbers are not public. In June 2023, four months before the liquidation, Néovacs still listed Signia among its holdings in a portfolio update. Signia is not in the EIC Fund's list of invested companies, which fits a grant-only award.

Why Europe Should Care

COVID-19 showed how few drugs Europe had against a new respiratory virus. The EU set up its Health Emergency Preparedness and Response Authority, HERA, to "ensure the development, manufacturing, procurement and equitable distribution of key medical countermeasures" for the next crisis. Broad-spectrum antivirals made from cheap, already-approved drugs are exactly the kind of tool that agenda needs, and Signia staff co-authored SARS-CoV-2 drug research published as early as July 2020.

The record also shows the weak spot of repurposing start-ups. Diltiazem is an old generic medicine, so the value lay in the platform and in clinical proof, and the clinical proof depended on academic hospital trials that the pandemic first slowed and then made unnecessary. Without trial data or a pharma partner, the platform alone did not attract the Series A the company sought.

The Verdict

Signia Therapeutics' former managers, its liquidator and the EIC have not been asked for comment for this article. It is based entirely on public records and published statements, linked throughout.