- Topline data from vafidemstat's PORTICO Phase IIb trial in Borderline Personality Disorder (BPD) reported with promising results in secondary endpoints of overall severity and control of agitation/aggression
- Company planning to request an End-of-Phase II meeting with the FDA to discuss plans for a registrational Phase III trial in BPD
- Continues to enroll patients in Phase IIb EVOLUTION trial with vafidemstat in schizophrenia
- Continues to recruit patients in FRIDA trial with iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients
- Research and development (R&D) expenses of
$3.9 and$16.6 million for the quarter and twelve months endedDecember 31, 2023 , respectively
Dr
Fourth Quarter and Recent Highlights
Vafidemstat in large multifactorial CNS indications:
- Topline results from PORTICO, 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, were reported onJanuary 5, 2024 . The primary endpoints, improvement in Borderline Personality Disorder Checklist (BPDCL) and in agitation/aggression by the Clinical Global Impression – Severity Agitation/Aggression (CGI-S A/A), did not reach statistical significance. However, nominal statistical significance was achieved on the secondary endpoint Borderline Evaluation of Severity (BEST), an overall measure of BPD disease severity, at weeks 8-12 (p = 0.042), with a relative reduction observed in the vafidemstat-treated group over the placebo group of 28.9%. Nominal statistical significance was also achieved on the secondary endpoint State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger, a measure of agitation and aggression, at weeks 8-12 (p = 0.026), with a relative reduction observed in the vafidemstat-treated group over the placebo group of 46.7%. Results across all primary and secondary efficacy endpoints consistently favored vafidemstat over placebo. Global Statistical Test (GST p-values) confirmed a consistent trend across efficacy endpoints. Vafidemstat was safe and well-tolerated. Adverse events (AEs) were generally consistent with the safety profile of vafidemstat seen to date, with no new safety findings. Based on the efficacy and safety results, Oryzon intends to request an end-of-Phase II meeting with the FDA to discuss plans for a registrational Phase III study for the treatment of BPD. The company is currently completing the full data analysis and plans to provide a full data presentation at a psychiatric conference later this year, as well as in a peer-reviewed 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 first cohort has been completed (six patients), and the combination was safe and showed strong antileukemic activity. The second cohort (six patients) is fully enrolled and ongoing. 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 Company is further expanding the clinical development of iadademstat in AML through an Investigator-initiated study (IIS). This trial will be a Phase Ib dose-finding study to evaluate iadademstat in combination with venetoclax and azacitidine in first-line AML patients, led by
Oregon Health & Science University (OHSU). The trial received FDA IND approval in 4Q2023 and is expected to begin enrolling patients in 1Q2024. - 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. - A new clinical trial of iadademstat in combination with an immune checkpoint inhibitor (ICI) in first-line metastatic SCLC, which will be conducted under the
Cooperative Research and Development Agreement (CRADA) signed with theNational Cancer Institute (NCI) inthe United States , is under preparation. This trial will be led by theMemorial Sloan Kettering Cancer Center (MSKCC), which plans to file the IND with the FDA in 1Q2024. - The STELLAR trial, a randomized, multicenter Phase Ib/II study of iadademstat plus a checkpoint inhibitor in first-line extensive-stage SCLC, will be informed and refined from the findings of the CRADA-MSKCC trial in the same space and with the same design that is expected to start in 1Q2024, as mentioned above. The company believes that STELLAR could potentially support an application for accelerated approval.
Earlier stage programs:
- ORY-4001, Oryzon’s highly selective histone deacetylase 6 (HDAC6) inhibitor nominated as a clinical candidate for the treatment of certain neurological diseases such as Charcot-Marie-Tooth disease (CMT), Amyotrophic Lateral Sclerosis (ALS) and others, is progressing through IND enabling studies to prepare it for clinical studies. The Company recently announced that is has received a
0.5 million USD grant from theALS Association in theU.S. to support the regulatory preclinical development of ORY-4001 for ALS. ORY-4001 has been previously shown 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. These results are fruit of a collaboration entered in 2022 between Oryzon and theCMT Research Foundation (CMTRF), aU.S. -based patient-led, non-profit organization focused on delivering treatments and cures for CMT. - Oryzon has received two new grants to further explore the role of epigenetic targets in the treatment of neuronal pathologies. These are two collaborative projects with public research centers, focused on the discovery and validation of novel biomarkers and epigenetic targets for the treatment of neuronal pathologies. The projects have a global budget of
2.3 million euros , of which Oryzon will receive up to1.4 million euros .
Financial Update: Fourth Quarter 2023 Financial Results
Research and development (R&D) expenses were
General and administrative expenses were
Net losses were
Negative net result was
Cash, cash equivalents and marketable securities totaled
BALANCE SHEET DATA (AUDITED)1 | |||
(Amounts in thousands US $) | |||
2023 | 2022 | ||
Cash and cash equivalents | 13,544 | 22,737 | |
Marketable securities | 0 | 0 | |
Total Assets | 118,125 | 110,606 | |
Deferred revenue | 12 | 0 | |
Total Stockholders' equity | 90,361 | 77,405 | |
STATEMENTS OF OPERATIONS (AUDITED)1 | |||||||
(US $, amounts in thousands except per share data) | |||||||
Three Months Ended | Twelve Months Ended | ||||||
2023 | 2022 | 2023 | 2022 | ||||
Collaboration Revenue | 0 | 0 | 0 | 0 | |||
Operating expenses: | |||||||
Research and Development | 3,867 | 5,033 | 16,631 | 18,050 | |||
General and administrative | 1,187 | 1,249 | 4,247 | 4,822 | |||
Total operating expenses | 5,054 | 6,282 | 20,878 | 22,872 | |||
Loss from Operations | -5,054 | -6,282 | -20,878 | -22,872 | |||
Other income, net | 3,619 | 4,693 | 15,851 | 17,016 | |||
Net Loss | -1,435 | -1,589 | -5,027 | -5,856 | |||
Net Financial & Tax | -468 | -863 | 1,322 | 1,342 | |||
Net Result | -1,903 | -2,452 | -3,705 | -4,514 | |||
Loss per share allocable to common stockholders: | |||||||
Basic | -0.03 | -0.05 | -0.06 | -0.08 | |||
Weighted average Shares outstanding | |||||||
Basic | 58,451,070 | 54,284,176 | 57,616,236 | 53,336,257 | |||
1 Spanish GAAP | |||||||
* Exchange Euro/Dollar (1.1050 for 2023 and 1.0666 in 2022) |
About Oryzon
Founded in 2000 in
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 differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see
About Vafidemstat
Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 has been observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity has also been observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Vafidemstat is being investigated in neuropsychiatric disorders in two double-blind, randomized, placebo-controlled Phase IIb trials: one in schizophrenia, named EVOLUTION (recruitment ongoing), and another one in Borderline Personality disorder (BPD), named PORTICO, recently finalized, with topline data and in the process of completing the full data analysis. Based on PORTICO’s topline results, the company is planning to request an End-of-Phase II meeting with the FDA to discuss options for a registrational Phase III trial in BPD. The company is also deploying a CNS precision medicine approach with vafidemstat in genetically-defined patient subpopulations of certain CNS disorders and is preparing a clinical trial in Kabuki Syndrome patients. The company is also exploring the clinical development of vafidemstat in other neurodevelopmental syndromes.
FORWARD-LOOKING STATEMENTS
This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del
IR, US | IR & Media, | Oryzon | |
Atrevia | Chief Business Officer | ||
+1 617 430 7577 | +41 78 680 05 38 | +34 91 564 07 25 +34 673 33 97 65 | +34 93 515 1313 |
arr@lifesciadvisors.com | svonderweid@lifesciadvisors.com | pcobo@atrevia.com mcordera@atrevia.com | etorrell@oryzon.com |
Source:
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