ORYZON reports financial results and corporate updates for quarter ended September 30, 2023

MADRID, SPAIN and BOSTON, MA, UNITED STATES, October 27^th, 2023 – Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company leveraging epigenetics to develop therapies in diseases with a strong unmet medical need, today reported financial results for the quarter ended September 30, 2023 and provided a corporate update on recent developments.

Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “Oryzon continued with a strong path in its clinical programs in the third quarter. In CNS, we recently reported positive blinded aggregate safety data of 198 patients from our Phase IIb PORTICO trial with vafidemstat in BPD at the ECNP conference earlier this month. BPD is a highly unmet medical need and an enormous commercial opportunity with limited competition and a low risk of generification. PORTICO is now fully enrolled, and we remain on track to present top-line data early next year. The company has started a structured dialogue with corporate pharma to identify a suitable partner to move forward the asset to Phase III, pending positive results. Our Phase IIb trial with vafidemstat in schizophrenia, EVOLUTION, has also continued to enroll patients. We continue working for a future submission of an IND to initiate HOPE in 2024, 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 make progress this quarter, with both iadademstat’s ongoing clinical trials, the FRIDA trial in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients, where a new cohort has been initiated, and the collaborative trial with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in neuroendocrine tumors, which is actively recruiting patients. In addition, and broadening our epigenetic pipeline, we reported positive preclinical efficacy data of ORY-4001, our selective HDAC-6 inhibitor recently nominated as a clinical development candidate, in Charcot-Marie-Tooth (CMT) at the Third Annual Global CMT Research Convention in Cambridge, U.S., and the medical team participated in several round tables.“

Third Quarter and Recent Highlights

Vafidemstat in large multifactorial CNS indications:

• Positive preliminary blinded aggregate safety data from PORTICO, vafidemstat’s Phase IIb clinical trial in BPD, reported at the 36th European College of Neuropsychopharmacology (ECNP) congress 2023, corresponding to the initial 198 randomized patients (data cut-off, August 23rd 2023). As of September 2023, PORTICO randomized 210 participants, and 131 of the originally planned participants (N = 150) already completed the trial. Results presented at ECNP 2023 confirm that PORTICO enrolled a representative real-world BPD population allowing common comorbidities and concomitant medications that are typically exclusionary in other BPD trials, as well as allowed subjects to receive psychotherapy during the trial. The screen failure and dropout rates were lower than in the most recent BPD clinical trial. Finally, the aggregated blinded safety data on the fully enrolled sample supports that vafidemstat has been extremely safe and well-tolerated, with a low discontinuation rate (2%) due to treatment-emergent adverse events (TEAEs) and 0% due to serious TEAEs (STEAEs). Only one serious TEAE deemed severe was reported, which fully recovered/resolved during the study. Current data of PORTICO continue to support that vafidemstat is safe and well-tolerated. Positive results from PORTICO’s interim analysis, conducted by the independent DMC in Q1 2023, were previously reported, with the trial being determined to be non-futile and to be continued with the planned enrollment number. PORTICO is a multicenter, double-blind, randomized, placebo-controlled Phase IIb conducted in the U.S. and EU 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 trial is fully recruited and last patient out is expected before the end of 2023. Topline results are expected in Q1 2024, followed by a full data presentation at a psychiatric conference, as well as in a peerreviewed journal publication.
• The EVOLUTION Phase IIb clinical trial with vafidemstat in patients with schizophrenia continues 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 continue the preparations of a new precision medicine trial in Kabuki Syndrome (KS). The company is in a dialogue with the regulatory agencies to refine the final design of this trial and expects to submit an IND for HOPE to the U.S. Food and Drug Administration (FDA) in 2024.

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+), continues 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 the 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 (MRD). The study is being conducted in the U.S. 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) continues to enroll patients. This trial is being conducted in the U.S. under a collaborative clinical research agreement with the FCCC, under which the FCCC will be conducting different collaborative combination clinical trials with iadademstat, with Oryzon providing funding, the drug, and technical expertise.
• Preparations for the STELLAR trial, a randomized, multicenter Phase Ib/II study of iadademstat plus a checkpoint inhibitor in first-line extensive-stage SCLC, are ongoing. The company believes that STELLAR could potentially support an application for accelerated approval.

Earlier stage programs:

• Positive preclinical efficacy data in CMT with ORY-4001, a selective histone deacetylase 6 (HDAC-6) inhibitor, was presented at the Third Annual Global CMT Research Convention held in September. ORY-4001 treatment was able to reverse disease progression symptoms in a CMT mice model which reliably recapitulates many of the symptoms of this condition in humans, improving myelination and restoring axon integrity in the sciatic nerve, and improving compound muscle action potential and nerve conduction in comparison with untreated animals. The results presented are fruit of a collaboration entered in 2022 between Oryzon and the CMT Research Foundation (CMTRF), a U.S.-based patient-led, non-profit organization focused on delivering treatments and cures for CMT. ORY-4001 was recently nominated as a clinical development candidate for the treatment of certain neurological diseases as CMT, Amyotrophic Lateral Sclerosis (ALS) and others, and the compound will now enter into IND enabling studies to prepare it for clinical studies. HDAC6 inhibitors have been previously proposed as potentially effective treatments for CMT, ALS and other neurological disorders that lack effective treatments.

Financial Update: Third Quarter 2023 Financial Results

Research and development (R&D) expenses were $3.8 and $12.2 million for the quarter and nine months ended September 30, 2023, respectively, compared to $4.3 and $11.9 million for the quarter and nine months ended September 30, 2022.

General and administrative expenses were $0.7 and $2.9 million for the quarter and nine months ended September 30, 2023, respectively, compared to $0.7 and $3.3 million for the quarter and nine months ended September 30, 2022.

Net losses were $0.8 and $3.4 million for the quarter and nine months ended September 30, 2023, respectively, compared to $0.7 and $3.9 million for the quarter and nine months ended September 30, 2022. The result is as expected, given the biotechnology business model where companies in the development phase typically have a long-term maturation period for products, and do not have recurrent income.

Negative net result was $1.7 million (–$0.03 per share) for the nine months ended September 30, 2023, compared to a negative net result of $1.9 million (–$0.04 per share) for the nine months ended September 30, 2022.

Cash, cash equivalents and marketable securities totaled $8.8 million as of September 30, 2023.