ORYZON Announces Publication of a relevant paper for the therapeutic development of Iadademstat (ORY-1001) in Small Cell Lung Cancer (SCLC)

Oryzon Genomics, S.A.(ISIN Code:ES0167733015,ORY), a public clinical-stage i o pharmaceutical company leveraging epigenetis to develop therapies indiseases with strong unmetmedical need, announced today the publication by US scientists of a newspaper in the February issue of Science Signaling, from the SCIENCEgroup (AAAS) describing how ORY-1001 (iadademstat) activates the NOTCH pathway, resulting in the repression of SCLC tumorigenes is in vitro and in patient-derived xenograft (PDX) models.

The paper, entitled"Targeting NOT CHactivation in smallcelllungcancerthroughLSD1inhibition" has been published by David Mac Pherson’s group at the Fred Hutchinson Cancer Research Centerand the Department of Genome Sciences, University of Washington, both in Seattle, WA, US and details how LSD1pharmacological inhibition with therapeutically-relevant doses of ORY-1001 results in the reactivation of the, in this context, tumor suppres orgene Notch, which causes the suppression of the transcription factor ASCL1, a protein activated in a majority of SCLC, resulting in the repression of SCLC tumorigenesis in vitro and in PDX models. This elucidation of the mechanism-of-action(MoA) is important: ASCL1has been characterized to play an important role in SCLC tumorigenesis butthis transcription factor is not classically “druggable”, ORY-1001 opens now a possibility to achieve this goal as its how sarobustanti-tumor effect in certain PDX models of SCLC with a favorable safety profile.

Dr. Tamara Maes, CSO of ORYZON, stated “This excellent paper provides a first detailed characterization of the Mo Athatallows SCLC tumors to be deactivated through LSD1inhibition and highlights the potential in this therapeutic indication ofORY-1001, with the observation of a clear anti tumor activity in certain PDX models”. “In Oryzon, we are firm believers in targeted therapies,and we have worked in recent years to identify biomarkers that we believe maybe behind these best responses too urdrug in SCLC and we have already started a clinical studyin SCLC patients that applies these biomarkers as inclusion criteria.” CLEPSIDRA ("A Combination trial of LSD1and Etop-Platinumin Small Cell Lung Cancerin Biomarker-ID Relapsed pAtients) is a PhaseIIa trial of Iadademstat that isbeing conducted in four hospitals in Spain. CLEPSIDRA enrols second line SCLC patients an dis designed as a single-arm,open-label study of Iadademstat in combination with the standard of care treatment platinum/e to poside,in order to evaluate the safety and tolerability as well as the clinical effect (including time to response, duration of response, objective response and overall survival) of the combination. The study is divided into two parts, the first one to optimize the dose of the combination and the second one to evaluate the efficacy of the combination.Approximately36 patients are planned to be recruited in this study.

The Science Signaling article may be found at: http://stke.sciencemag.org/content/sigtrans/12/567/eaau2922.full.pdf

About Oryzon

Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code:ES0167733015) is a clinical stage bio pharmaceutical company considered as the European champion in Epigenetics. Oryzon has one of the strongest portfolios in the field. Oryzon’s LSD1 program has rendered two compounds Vafidemstat and Iadademstat in clinical trials. In addition, Oryzon has ongoing programs for developing inhibitors against other epigenetic targets. Oryzon has a strong technological platform for biomarker identification and performs biomarker and target validation for a variety of malignant and neuro degenerativediseases. Oryzon has offices in Spain and the United States. For more information, visit www.oryzon.com

About Iadademstat

Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful different iating effect in hematologic cancers (SeeMaesetal.,CancerCell2018Mar12;33(3):495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A first Phase I/IIa clinical trial with Iadademstat in refractory and relapsed acute leukemia patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), medullo blastoma and others. Oryzon has recently started two Phase IIa clinical trials of Iadademstat in combination; the first one in combination with Azacitidine in elderly AML patients (ALICEstudy) and the second one in combination with platinum/e top oside in second line SCLC patients (CLEPSIDRA study).