Cash, cash equivalents and marketable securities totaled $22.7 million as of December 31, 2022

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 fourth quarter ended December 31, 2022 and provided an update on recent developments.

Dr Carlos Buesa, Oryzon’s Chief Executive Officer, said: “We continued to make robust progress on our clinical development this quarter. The final data from iadademstat’s Phase II trial in acute myeloid leukemia (AML) reported at ASH confirmed not only a robust percentage of rapid and durable responses alongside good tolerability but, interestingly we also observed clinical responses in myelomonocytic AML patients, and in other patients harboring adverse prognose mutations such as p53+ who usually respond poorly to current therapies. We believe combination approaches with iadademstat will increase therapeutic options for AML patients both in first and second line. Our new FRIDA trial with iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients is now the company’s central strategy and, we believe, our fastest route to market. 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.”

Dr Buesa continued, “In CNS, we also made strong progress. We continue to actively recruit patients in the Phase IIb PORTICO trial with vafidemstat in Borderline Personality Disorder in the US and Europe, and expect to conclude the planned interim analysis by end of the first quarter this year. BPD is a highly unmet medical need and an enormous commercial opportunity with limited competition. Enrollment continues to progress in our second Phase IIb EVOLUTION trial in schizophrenia. Furthermore, we continue with our plan to initiate HOPE this year, the first randomized Phase I/II personalized medicine trial with an LSD1 inhibitor, in Kabuki Syndrome patients.”

Fourth Quarter and Recent Highlights

Iadademstat in oncology:

Final data from the recently completed Phase II ALICE trial, which investigated iadademstat in combination with azacitidine in elderly or unfit AML patients, were presented as an oral communication at the ASH congress in December 2022. The presentation was also shortlisted for inclusion in the final lists of “Highlights of ASH” in the AML Section. Clinical efficacy signals were robust, with ORR of 81%, where 64% of the responders showed a CR/CRi, as well as a good safety profile for the combination of iadademstat and azacitidine. Responses were deep and durable, with 68% of the CR/CRi lasting over 6 months and 71% of CR/CRi achieving transfusion independence, and rapid (by two months). Three patients remained on study for more than 1 year, 2 patients for more than 2 years and 1 patient for more than 3 years. Responses were seen in patients with a diverse array of AML mutations, suggesting a broad applicability for iadademstat in AML. All FLT3+ patients included in ALICE (100%; 3 out of 3) and a high proportion of TP53+ patients (75%; 6 out of 8) responded; patients with monocytic AML subtypes (M4/M5) also showed high response levels (86%; 6 out of 7).

Oryzon completed the preparations to start FRIDA which is now ready to recruit. FRIDA is a Phase Ib clinical trial in patients with relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) harboring a FMS-like tyrosine kinase mutation (FLT3mut+), which has already received IND approval from the FDA. FRIDA is an open-label, multicenter study of iadademstat plus gilteritinib for the treatment of patients with R/R AML with FLT3 mutations. The primary objectives 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 will accrue up to approximately 45 patients and 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.

 A 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 been recently initiated. 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.

The company has been awarded an EU grant under the Eurostars-3 program to further explore the role of iadademstat in oncological immunotherapy approaches. This funding has been awarded to the BRAVE Project (Breaking immune Resistance of Advanced cancers by HERV-K Vaccination and Epigenetic modulation), which will be developed in collaboration with the Danish company ImProTher and the University of Copenhagen, which will evaluate the role of iadademstat in several immunotherapy strategies, including checkpoint inhibitors and/or oncological vaccines, in solids tumors. The project is expected to start on May 1, 2023, with a duration of two years, and has a global budget of 1.4 million euros, with Oryzon contributing approximately 50%.

Vafidemstat in large multifactorial CNS indications:

The PORTICO Phase IIb clinical trial with vafidemstat in patients with Borderline Personality Disorder (BPD) 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 will include 156 patients, with 78 patients in each arm. Preliminary blinded aggregate safety data from the first randomized 43 patients were presented at the 10th European Conference on Mental Health (ECMH) in 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. An independent interim analysis to assess the signal size and futility is expected to be done in 1Q23 with the data of the first 90 patients that will have concluded at least 2/3 of the trial.

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.

Financial Update: Fourth Quarter 2022 Financial Results

Research and development (R&D) expenses were $5.0 and $18.1 million for the quarter and twelve months ended December 31, 2022, compared to $3.9 and $14.8 million for the quarter and twelve months ended December 31, 2021.

General and administrative expenses were $1.2 and $4.8 million for the quarter and twelve months ended December 31, 2022, compared to $2.0 and $5.4 million for the quarter and twelve months ended December 31, 2021.

Net losses were $1.6 and $5.9 million for the quarter and twelve months ended December 31, 2022, compared to $2.4 and $7.9 million for the quarter and twelve months ended December 31, 2021. 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 $4.5 million (-$0.085 per share) for the twelve months ended December 31, 2022, compared to a negative net result of $5.3 million (-$0.101 per share) for the twelve months ended December 31, 2021.

Cash, cash equivalents and marketable securities totaled $22.7 million as of December 31, 2022.