ORYZON reports financial results and corporate update for quarter ended March 31, 2023

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 ended March 31, 2023 and provided an update on recent developments.

Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “Oryzon has made strong clinical progress in the first quarter this year. In CNS, we reported positive results from the planned interim analysis in the Phase IIb PORTICO trial with vafidemstat in Borderline Personality Disorder (BPD), with the trial being determined as non-futile and to be continued with the planned enrollment number. BPD is a highly unmet medical need and an enormous commercial opportunity with limited competition. We are continuing to actively recruit patients in PORTICO in the U.S. and Europe, and we expect to analyze top-line data at the end of this year or early next year. Enrollment also continues to progress in our Phase IIb EVOLUTION trial with vafidemstat in schizophrenia. Furthermore, we are on track to submit the IND to initiate HOPE this year, the first randomized Phase I/II personalized medicine trial with an LSD1 inhibitor, in Kabuki Syndrome patients.”

Dr Buesa continued: “In oncology, we also continued to progress our clinical pipeline this quarter. Recruitment has commenced in the new FRIDA trial with iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients. This is now the company’s central strategy and, we believe, our fastest route to market for iadademstat. We are also extremely excited with the recent initiation of a collaborative trial with the Fox Chase Cancer Center (FCCC) in the US in neuroendocrine tumors. This collaboration with the Cancer Epigenetics Institute at Fox Chase Cancer Center, a center of excellence for research in both Neuroendocrine Cancers and epigenetics, is part of an ambitious project to explore LSD1 therapeutic potential in neuroendocrine tumors.”

First Quarter and Recent Highlights

Iadademstat in oncology

• FRIDA, an open-label, multicenter Phase Ib clinical trial of iadademstat in combination with gilteritinib in patients with relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), has started to enroll patients. The primary objectives of the trial are to evaluate the safety and tolerability of iadademstat in combination with gilteritinib in patients with FLT3mut+ R/R AML and to establish the Recommended Phase 2 Dose (RP2D) for this combination. Secondary objectives include evaluation of the treatment efficacy, measured as the rate of complete remission and complete remission with partial hematological recovery (CR/CRh), the Duration of Responses (DoR) and the assessment of Measurable Residual Disease. The study is being conducted in the USA and will accrue up to approximately 45 patients. If successful, Oryzon and the FDA have agreed to hold a meeting to discuss the best plan to further develop this combination in this much in need AML population.
• The collaborative Phase II basket trial of iadademstat in combination with paclitaxel in platinum R/R small cell lung cancer (SCLC) and extrapulmonary high grade neuroendocrine tumors (NET trial) has continued to enroll patients. This trial is conducted in the US under a collaborative clinical research agreement with the Fox Chase Cancer Center (FCCC), under which the FCCC will be conducting different collaborative combination clinical trials with iadademstat, with Oryzon providing funding, the drug and technical expertise. The IND for this trial was approved by the FDA in November 2022 and the first patient was enrolled in January 2023.
• Preparations for new trials in combination in solid tumors are continuing. In SCLC, the STELLAR trial a randomized, multicenter Phase Ib/II study of iadademstat plus a checkpoint inhibitor in first line extensive-stage SCLC is being prepared. The company believes that STELLAR could potentially support an application for accelerated approval.

Vafidemstat in large multifactorial CNS indications

• Positive results obtained in the interim analysis of PORTICO, a Phase IIb clinical trial with vafidemstat in patients with Borderline Personality Disorder (BPD). These results were determined by an Independent Data Monitoring Committee (IDMC) on March 30, 2023 based on the efficacy and safety data of the first 90 patients who completed treatment, with the trial being determined to be non-futile and to be continued with the planned enrollment number . The trial has continued to actively enroll patients in Europe and the US. 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 independent primary objectives: reduction of aggression/agitation and overall BPD improvement. The study aims to include about 188 patients, distributed between two arms. Preliminary blinded aggregate safety data from the first randomized 43 patients were previously presented at the 10th European Conference on Mental Health (ECMH) last September. There were no reported serious adverse events. Forty-one adverse reactions, affecting 12 patients treated either with vafidemstat or placebo were reported, most of them mild and none reported as severe, with none leading to treatment discontinuation or patient withdrawal. PORTICO safety data is aligned with aggregated safety data collected from different vafidemstat clinical trials, in which more than 370 subjects have been treated with the drug. Current data of PORTICO continue to support that vafidemstat is safe and well-tolerated.
• The EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia has continued to enroll patients. This Phase IIb study aims to evaluate the efficacy of vafidemstat on negative symptoms and cognitive impairment in patients with schizophrenia. This project is partially financed with public funds from the Spanish Ministry of Science and Innovation and is being carried out in various Spanish hospitals.

Vafidemstat in monogenic CNS indications

• We are finalizing the preparation of a new precision medicine trial in Kabuki Syndrome (KS). This Phase I/II trial, named HOPE, will be a multicenter, multi-arm, randomized, double-blind and placebo-controlled trial to explore the safety and efficacy of vafidemstat in improving several impairments described in KS patients. The trial plans to enroll 50-60 patients and will be carried out in several hospitals and sites in the United States and, possibly, in Europe. The company is in a dialogue with the regulatory agencies to refine the final design of this trial and expects to submit the IND for HOPE to the FDA in 2023.
• Our precision medicine programs in psychiatric disease continue to progress. We have collaborations in autism with researchers at the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai Hospital in New York and the Institute of Medical and Molecular Genetics (INGEMM) at Hospital Universitario La Paz of Madrid and in schizophrenia with researchers from Columbia University in New York. The results of the ongoing pilot studies to characterize patients with specific mutations to inform subsequent precision psychiatry clinical trials with vafidemstat are ongoing.

Earlier stage programs

ORY-4001, a selective histone deacetylase 6 (HDAC-6) inhibitor, nominated as clinical development candidate for the treatment of certain neurological diseases as Charcot-Marie-Tooth (CMT), Amyotrophic Lateral Sclerosis (ALS) and others. HDAC6 inhibitors have been previously proposed as potentially effective treatments for CMT, ALS and other neurological disorders that lack effective treatments. In 2022, Oryzon and the CMT Research Foundation (CMTRF), a U.S.-based patient-led, non-profit organization focused on delivering treatments and cures for CMT, entered into an agreement to explore Oryzon’s HDAC-6 inhibitors in CMT models. ORY-4001 has shown multiple positive responses in a validated CMT1A peripheral neuropathy in vivo model which reliably recapitulates many of the symptoms of this condition in humans. ORY-4001 will enter now into IND enabling studies to prepare the compound for clinical studies.

More information in the attached file.