ORYZON reports results and corporate update for quarter ended March 31, 2021

MADRID, SPAIN and CAMBRIDGE, MA, UNITED STATES, May 7^th, 2020 – Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with strong unmet medical need, today reported financial results for the first quarter of 2021 and provided an update on recent developments.

Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “Oryzon continued to make strong progress in our pioneering work in personalized medicine in epigenetics during the first quarter. The enrollment of our first patient in the Phase IIb study with vafidemstat in borderline personality disorder and the ongoing collaborations in precision medicine with Columbia University, Seaver Autism Center at Mount Sinai and INGEMM are significant steps forward in our epigenetic approach to CNS. The Phase II trial ALICE, investigating iadademstat in combination with azacitidine in acute myeloid leukemia, continues recruitment and is progressing as planned. We finished the first quarter with a reinforced cash position of $45.2 million, which provides funding for the further development of our exciting pipeline until 1Q 2023.”

First Quarter and Recent Highlights

Iadademstat in oncology:

• The ongoing Phase II trial ALICE, investigating iadademstat in combination with azacitidine in acute myeloid leukemia (AML), continues recruitment. Preliminary results for this trial, last presented at the ASH-2020 conference, show robust signals of clinical efficacy, with 85.7% of reported objective responses, of which 58.3% are complete remissions (CR/CRi). Long responses are maturing, with 4 patients in response already for > 1 year, and the longest remission > 2 years (still ongoing). Of patients with > 120 days on treatment, 40% have overcome their dependency on blood transfusions. Iadademstat and azacitidine combination appears to be safe and well tolerated. The company plans to provide a new clinical update on ALICE at the European Hematology Association (EHA)-2021 conference.
• FDA Orphan Drug Designation granted to iadademstat for the treatment of AML. The drug now has orphan designation in both U.S. and EU.
• New trials in combination in AML and solid tumors are under preparation. The company believes that there is potential for fast market regulatory paths in both areas. Oryzon expects to announce further details in 2H 2021.

Vafidemstat in neurological and inflammatory disease:

• Started patient enrollment in the Phase IIb clinical trial with vafidemstat in patients with Borderline Personality Disorder (BPD). The study, named PORTICO, is a multicenter, double-blind, randomized, placebo-controlled Phase IIb to evaluate the efficacy and safety of vafidemstat in BPD patients. The trial has two primary objectives: reduction of aggression/agitation and overall BPD improvement. The study will include 156 patients, with 78 patients in each arm, and has a pre-defined interim analysis to adjust the sample size in case of excessive variability around the endpoints or an unexpectedly high placebo rate. Sites in the U.S., Spain and at least two other European countries will participate in the trial, with three Spanish hospitals activated in the first stage. Following a successful pre-IND meeting with the U.S. FDA, Oryzon will proceed to file an IND application in 2Q 2021.
• Submitted Clinical Trial Application (CTA) to the Spanish Medicine Agency (AEMPS) for a new Phase IIb clinical trial (EVOLUTION) to evaluate vafidemstat’s efficacy on negative symptoms and cognition in schizophrenia patients. Dosing of the first patient is expected in 1H 2021. This project is partly funded by public funds from the Spanish Ministry of Science and Innovation and will be performed in collaboration with the Research Institute of Vall d’Hebrón (VHIR) in Barcelona.
• Entered preclinical collaboration on autism with researchers from the Seaver Autism Center at the Icahn School of Medicine at Mount Sinai led by Dr. Joseph Buxbaum. This collaboration will explore the effects of vafidemstat in animal models defective for Shank3 developed and characterized by the team of Dr. Buxbaum, which recapitulate many symptoms of a variety of autism known as Phelan-McDermid Syndrome (PMS). Deletions or mutations at the end of chromosome 22 lead to a defect of the Shank3 gene and produce PMS in humans. This collaboration is complementary to the work the company is already undertaking in the field of precision medicine in PMS in collaboration with the Institute of Medical and Molecular Genetics (INGEMM) of the La Paz University Hospital in Madrid. A pilot study is ongoing with INGEMM to phenotypically characterize up to 40 PMS patients using a battery of validated scales in the field. Results of this pilot study are expected in 3Q 2021. The aim is that this cognitive, behavioral and functional baseline assessment of PMS patients will inform a future clinical study with vafidemstat.
• The precision medicine collaboration in schizophrenia with researchers from Columbia University in New York is advancing. The goal is to perform an exhaustive functional psychometric characterization of up to 60 individuals carrying mutations in the Setd1a gene to build a foundation for a subsequent precision psychiatry clinical trial with vafidemstat for SETD1A-associated psychiatric disorders. Results of this characterization study are expected in 3Q 2021. SETD1A is a histone methyltransferase that is a key schizophrenia susceptibility gene.
• ETHERAL 12 month data presented at the AD/PD-2021 virtual conference, confirming the safety of vafidemstat treatment in the elder population with Alzheimer’s Disease (AD) in the aggregated data of 140 patients. The reduction of CSF levels of the inflammatory YKL40 biomarker was also confirmed after 12-month vafidemstat treatment. Additional data from the REIMAGINE-AD trial were also presented, confirming a significant reduction in agitation-aggression after 12-month treatment in moderate AD patients.
• Finalized recruitment in the ongoing study in severe Covid-19 patients, named ESCAPE. This is an open-label, randomized, double arm Phase II trial to assess the efficacy and tolerability of vafidemstat in combination with standard of care, to prevent progression to Acute Respiratory Distress Syndrome (ARDS). The study was initially designed to recruit 40 patients but was later upsized to 60. Analysis of data is ongoing and preliminary results are expected in 1H 2021.

Financial Update: First Quarter 2021 Financial Results

Research and development (R&D) expenses were $4.3 million for the last 3 months ended March 31, 2021 at the same level for the last 3 months ended March 31, 2020.

General and administrative expenses were $1.30 million for the last 3 months ended March 31, 2021 compared to $0.85 million for the last 3 months ended March 31, 2020.

Net losses were $2.04 million for the last 3 months ended March 31, 2021 compared to net losses of $1.15 million for the last 3 months ended March 31, 2020. This is due to a higher investment in research and non-capitalized development of the ESCAPE clinical trial and non-recurring expenses. The result is in accordance with the specificity of the biotechnology business model, in the development phase of the Company, with a long-term maturation period for its products, and without recurrent income.

Negative net result of $2.13 million (-$0.04 per share) for the last 3 months ended March 31, 2021, compared to a negative net result of $1.27 million (- $0,03 per share) for the 3 months ended March 31, 2020.

Cash, cash equivalents and marketable securities totaled $45.2 million as of March 31, 2021, compared to $32.1 million as of March 31, 2020.