Theranexus

Regulatory Filings • Apr 23, 2024

Theranexus, Diverchim and Inserm awarded €4.7 million in funding under the "Innova>ons in biotherapies and biomanufacturing" call for proposals from France 2030 to develop a novel an>sense oligonucleo>de

Lyon, April 23rd, 2024

Sponsors of the PickASO project, a winner of the "Innova9ons in biotherapies and biomanufacturing" call for proposals from France 2030, Theranexus, Diverchim and Inserm's ARNA laboratory were awarded €4.7 million in funding from French Governement to develop a revolu9onary autophagy ac9va9on therapy.

The PickASO consor9um is led by Theranexus, a specialist in rare neurological diseases, and will include Diverchim, expert in the synthesis of ac9ve pharmaceu9cal ingredients, and Inserm's ARNA laboratory, France's leading academic ins9tu9on in the field of an9sense oligonucleo9des (ASOs).

PickASO won the "Innova9ons in biotherapies and biomanufacturing" call for proposals under the France 2030 investment plan. The €4.7 M, 3-year funding package is aUributed by the French government and operated by Bpifrance and breaks down into grants and repayable advances. With this funding Theranexus will handle development (up to entry into clinical development) of an an9sense oligonucleo9de, an innova9ve drug candidate targe9ng TFEB1 , the protein iden9fied as the autophagy2 regulator. The project draws on Theranexus' capabili9es in the areas of molecular biology, neuroscience and drug development and ARNA and Diverchim's exper9se in RNA chemistry and industrial ac9ve ingredient synthesis, respec9vely.

"We sincerely thank the French governement for it financial support via France 2030 for the PickASO project. In line with our major strategic shiC to rare neurological diseases iniEated two years ago, via this collaboraEon with two leading players, Theranexus will be the first company to develop and bring to clinical trials an anEsense oligonucleoEde targeEng a central autophagy pathway – the TFEB pathway – for paEents with rare neurological diseases", explained Theranexus Chairman and CEO, Mathieu Charvériat.

"The PickASO project is an opportunity for Inserm (ARNA unit) to showcase its experEse in the area of oligonucleoEdes for therapeuEc applicaEons and give internaEonal visibility to its Optoligo plaRorm. Moreover, this project will allow Inserm to validate and illustrate the value of its innovaEons in the fields of bioconjugaEon and modificaEon of nucleic acids, notably in the development of therapies targeEng rare neurological diseases. In terms of commercializaEon, the transfer of patents developed at Inserm to French industries and biotech firms will foster the development of new technologies essenEal for the drug candidates of tomorrow", said Philippe Barthélémy, Director of the Inserm ARNA unit.

¹ The protein TFEB is the recognized molecular switch for autophagy; its ac;va;on has been reported as an effec;ve therapeu;c remedy for numerous diseases, as shown in various in vitro or in vivo models.

² Autophagy is a cellular process involving small intracellular vesicles known as lysosomes used by cells to recycle part of their own material and destroy certain residues which accumulate and may become toxic for them.

"At Diverchim, we are very excited to collaborate on the PickASO project with such presEgious players as Theranexus and Inserm. Diverchim will be the first French company to offer ASO producEon capability that meets Good Manufacturing PracEces(GMP) requirements to manufacture clinical and commercial batches. We see this collaboraEon as a unique opportunity to apply our experEse to a novel therapy. The combinaEon of our experEse in the chemistry of acEve pharmaceuEcal ingredients and the cuYngedge capabiliEes of our partners promises significant advances in biotherapies. We are looking forward to tackling this challenge together and to helping provide innovaEve soluEons to paEents in need", con9nued Diverchim CEO, François Macarez.

"The PickASO project embodies the collecEve commitment to offer new hope to paEents with lysosomal diseases and boost the excellence of research and innovaEon in innovaEve therapies in France. Over and above this development, the PickASO project aims to structure a producEon sector for anEsense oligonucleoEdes as there is currently none available in France for this very promising molecule that has great potenEal for the booming internaEonal market. This project is completely in the spirit of what the State is pursuing with France 2030, and in parEcular the health aspect: supporEng and supporEng health innovaEon to strengthen our sectors and our producEon capaciEes, and thus regain our sovereignty in health » specifies Bruno Bonnell, general secretary for investment in charge of France 2030.

TFEB, an autophagy regulator

Autophagy is a cellular process involving small intracellular vesicles known as lysosomes used by cells to recycle part of their own material and destroy certain residues which accumulate and may become toxic for them. This process, which earned the Japanese scien9st Yoshinori Ohsumi the Nobel Prize in 2016, is essen9al for cell and par9cularly neuron func9on, and is disrupted in a group of rare diseases called lysosomal diseases. Niemann-Pick type C, Sanfilippo and BaUen diseases are examples of lysosomal diseases. But beyond these rare diseases, autophagy generally decreases with age and an autophagy deficiency is now iden9fied as a determinant of diseases such as Parkinson's, amyotrophic lateral sclerosis (ALS) or age-related macular degenera9on (AMD). The protein TFEB is the recognized molecular switch for autophagy3 ; its ac9va9on has been reported as an effec9ve therapeu9c remedy for numerous diseases, as shown in various in vitro or in vivo models.

Overview of the PickASO project

Firstly, Theranexus had already iden9fied an ASO promo9ng autophagy via direct ac9on on TFEB. The first step in the PickASO project will involve assessing Inserm's lipid conjuga9on technology for improving the pharmacokine9c profile of ASOs and their ability to penetrate cells. Meanwhile Diverchim and Inserm will work together to implement semi-automated GMP (Good Manufacturing Prac9ce)-compliant produc9on of this ASO; and this will be a big first for France. Theranexus will also handle regulatory preclinical characteriza9on. On project comple9on, the drug candidate's formula9on will be approved, paving the way for clinical development.

About Theranexus

Theranexus is an innova.ve biopharmaceu.cal company that emerged from the French Alterna.ve Energies and Atomic Energy Commission (CEA). It specializes in the treatment of rare neurological diseases. The company has a unique plaCorm for the iden.fica.on and characteriza.on of advanced therapy drug candidates targe.ng rare neurological disorders and an ini.al drug candidate in clinical development for BaFen disease.

Theranexus is listed on the Euronext Growth market in Paris (FR0013286259 - ALTHX).

Press contact: Florence Portejoie, FP2COM, fportejoie@fp2com.fr, +33 (0)6 07 76 82 83

³ https://pubmed.ncbi.nlm.nih.gov/33259088/;https://pubmed.ncbi.nlm.nih.gov/27252382/

About Diverchim

Diverchim is a renowned specialist in the synthesis of sophis.cated small-scale organic molecules. As a high value-added service provider for the pharmaceu.cal, cosme.cs and biotechnology industries for over two decades, Diverchim offers its clients an extensive range of services from design and manufacturing of ac.ve substances to the drabing and filing of regulatory applica.ons.

Communica/on contact: Marc Panic, Seriana, marc.panic@seriana.fr

About Inserm

The ARNA laboratory (Nucleic Acids: Natural and Ar.ficial Regula.ons) in Bordeaux includes approximately 120 researchers across 6 interdisciplinary teams (chemistry, biology, biophysics) and 3 core facili.es, half of which are permanent staff of Inserm, the CNRS and the University of Bordeaux (INSERM U1212 / UMR CNRS 5320, UB, hFps://arna.cnrs.fr). ARNA is a structure unique to Europe that implements research focused on the study of nucleic acids. The laboratory boasts exper.se that is unique to France and offers proprietary oligonucleo.de bioconjuga.on technologies to improve the pharmacological and biodelivery proper.es of ASOs, as shown through numerous collabora.ons.

About France 2030

• Governed by Bruno Bonnell Secretary General of Investments (SGPI) on behalf of the Prime Minister.
• A double ambition: Sustainably transform our key economic sectors (energy, healthcare, automobile, aeronautics, space…) whilst increasing the competitivity of French companies in these respective sectors. France 2030 will support all cycles of innovation up until industrialisation: from research to development of ideas, to prototypes, to production of new services and products.
• Unprecedent funding: €54 billion will be invested into companies, universities and research centers. France 2030 is in possession and has control over its €54 billion fund and will invest 50% of the budget into the decarbonisation of French economy and the latter 50% in sustainable innovations and ground-breaking technologies.
• Collective action: Strategic actions and plans will be thought of and deployed in coordination with economic actors, academia and field experts, as well as local and European institutions.

For more informa+on: h.ps://www.gouvernement.fr/france-2030

About Bpifrance

About Bpifrance Bpifrance Inves.ssement is the management company that handles Bpifrance's equity investments. Bpifrance is the French na.onal investment bank: it finances businesses – at every stage of their development – through loans, guarantees, equity investments and export insurances. Bpifrance also provides extra financial services (training, consultancy) to help entrepreneurs meet their challenges (innova.on, export…). For more informa.on, please visit: hFps://www.bpifrance.com/

Follow us on TwiFer: @Bpifrance - @BpifrancePresse

Disclaimer

This press release contains certain forward-looking statements concerning Theranexus and its business, including its prospects and product candidate development. Such forward-looking statements are based on assumptions that Theranexus considers to be reasonable. However, there can be no assurance that the estimates contained in such forward-looking statements will be verified, which estimates are subject to numerous risks including the risks set forth in the universal registration document of Theranexus filed with the AMF on 27 April 2023 under number D.23-0345 (a copy of which is available on www.theranexus.com) and to the development of economic conditions, financial markets and the markets in which Theranexus operates. The forward-looking statements contained in this press release are also subject to risks not yet known to Theranexus or not currently considered material by Theranexus. The occurrence of all or part of such risks could cause actual results, financial conditions, performance or achievements of Theranexus to be materially different from such forward-looking statements. Theranexus expressly declines any obligation to update such forward-looking statements.