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2 July 2014 EMA/COMP/228647/2014 Committee for Orphan Medicinal Products Autologous dendritic cells pulsed with RNA from glioma stem cells for the treatment of glioma On 4 June 2014, orphan designation (EU/03/14/1273) was granted by the European Commission to Epitarget AS, Norway, for autologous dendritic cells pulsed with RNA from glioma stem cells for the treatment of glioma. What is glioma? Glioma is a type of brain tumour that affects the glial cells (the cells that surround and support the nerve cells). Patients with glioma can have severe symptoms, but the types of symptoms experienced depend on where the tumour develops in the brain. Symptoms can include headaches, nausea (feeling sick), loss of appetite, vomiting, and changes in personality, mood, mental capacity and concentration. About a fifth of patients with glioma have seizures (fits) for months or years before the disease is diagnosed. Glioma is a long-term debilitating and life-threatening disease because of the severe damage to the brain, and is associated with poor long-term survival. What is the estimated number of patients affected by the condition? At the time of designation, glioma affected approximately 2.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 112,000 people *, and is below the ceiling for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP). What treatments are available? At the time of designation, several medicines were authorised for the treatment of glioma in the EU. Treatments for glioma included surgery, radiotherapy (treatment with radiation), and chemotherapy * Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014). 7 Westferry Circus Canary Wharf London E14 4HB United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8416 E-mail info@ema.europa.eu Website www.ema.europa.eu An agency of the European Union European Medicines Agency, 2014. Reproduction is authorised provided the source is acknowledged.

(medicines to treat cancer) to improve survival. Patients also received treatments for the symptoms of glioma, including corticosteroids to reduce pressure within the skull and medicines to prevent seizures. The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with glioma because early clinical studies showed that the medicine increased progression-free survival (how long patients lived without their disease getting worse) of patients when given in combination with currently authorised treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status. How is this medicine expected to work? This medicine is expected to work by activating the patient s immune system (the body s natural defences) so that it attacks and kills the cancer cells. The medicine is prepared from the patient s own (autologous) immune cells called dendritic cells. These cells are mixed in the laboratory with genetic material from stem cells from the patient s glioma (cells from which the glioma is believed to originate and propagate). When the dendritic cells are injected back into the patient, it is expected that they will help the immune system recognise the patient s glioma cells as foreign and stimulate an immune response against them, helping to slow down or stop the progression of the disease. What is the stage of development of this medicine? At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with glioma were ongoing. At the time of submission, the medicine was not authorised anywhere in the EU for glioma or designated as an orphan medicinal product elsewhere for this condition. In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 April 2014 recommending the granting of this designation. Opinions on orphan medicinal product designations are based on the following three criteria: the seriousness of the condition; the existence of alternative methods of diagnosis, prevention or treatment; either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment. Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation. EMA/COMP/228647/2014 Page 2/5

For more information Sponsor s contact details: Epitarget AS Oslo Science Park Gaustadalléen 21 0349 Oslo Norway E-mail: mail@epitarget.com For contact details of patients organisations whose activities are targeted at rare diseases see: Orphanet, a database containing information on rare diseases, which includes a directory of patients organisations registered in Europe; European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases. EMA/COMP/228647/2014 Page 3/5

Translations of the active ingredient and indication in all official EU languages 1, Norwegian and Icelandic Language Active ingredient Indication English Bulgarian Croatian Czech Danish Dutch Estonian Finnish French German Greek Hungarian Italian Latvian Lithuanian Maltese Polish Portuguese Romanian Slovak Autologous dendritic cells pulsed with RNA from glioma stem cells Автоложни дендритни клетки, натоварени с РНК от глиомни стволови клетки Autologne dendritičke stanice podražene s RNK iz matičnih stanica glioma Autologní dendritické buňky pulzované RNA z kmenových buněk gliomu Autologe dendritiske celler pulset med RNA fra gliom stamceller Autologe dendritische cellen gepulseerd met RNA afkomstig van glioma stamcellen Glioomi tüvirakkude RNA-ga laetud autoloogsed dendriitrakud Gliooman kantasolujen RNA:lla ladatut autologiset dendriittisolut Cellules dendritiques autologues chargées en ARN des cellules souches gliomales Autologe dendritische Zellen, die mit Gliomastammzellen-RNS behandelt wurden Αυτόλογα δενδριτικά κύτταρα επωασμένα με RNA από βλαστοκύτταρα γλοιώματος Glióma őssejtekből származó RNS-sel pulzált autológ dendritikus sejtek Cellule dendritiche autologhe pulsate con RNA di cellule staminali di glioma Ar RNS no gliomas cilmes šūnām pārslogotas autologās dendrītu šūnas Autologinės dendritinės ląstelės pripildytos gliomos kamieninių ląstelių RNR Ċelluli dendritiċi awtologużi pulsati ma RNA minn ċelluli staminali tal-glioma Autologiczne komórki dendrytowe obładowane RNA z komórek macierzystych glejaka Células dendríticas autólogas carregadas com ARN de células estaminais de glioma Celule dentriceautologe încărcate cu ARN extras din celule stem de gliom Autológne dendritické bunky pulzované RNA z kmeňových buniek gliómu Treatment of glioma Лечение на глиома Liječenje glioma Léčba gliomů Behandling af gliom Behandeling van glioma Glioomi ravi Gliooman hoito Traitement des gliomes Behandlung von Gliomen Θεραπεία του γλοιώματος Glioma kezelése Trattamento del glioma Gliomas ārstēšana Gliomos gydymas Kura tal-glioma Leczenie glejaka Tratamento do glioma Tratamentul gliomului Liečba gliómu 1 At the time of designation EMA/COMP/228647/2014 Page 4/5

Language Active ingredient Indication Slovenian Spanish Swedish Norwegian Icelandic Avtologne dendritične celice pulzirane z RNK matičnih gliomskih celic Células dendríticas autólogas impulsadas con ARN de las células madre del glioma Autologa dendritiska celler pulserade med RNA från gliomstamceller Autologe dendrittiske celler pulset med RNA fra stamceller fra gliomer Samgena griplufrumur hlaðnar RNA úr glíóma stofnfrumum Zdravljenje glioma Tratamiento del glioma Behandling av gliom Behandling av gliom Meðferð á glíóma EMA/COMP/228647/2014 Page 5/5