Iadademstat

Selected for oral presentation Conference will be held in Milan on September 21-23 June 26, 2024 -- 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 announced that it will present final data from its Phase IIb PORTICO trial, which investigated the efficacy of vafidemstat in the treatment of Borderline Personality Disorder (BPD), as an oral presentation at the 37th European College of Neuropsychopharmacology (ECNP) annual conference, to be held on September 21-23, 2024 in Milan, Italy. Dr. Michael Ropacki, Oryzon’s Chief Medical Officer, Head of CNS Clinical Development, will be presenting the results at the ECNP New Medication Symposium on September 23rd. The oral communication is entitled “Final Results: PORTICO a double-blind, randomized placebo-controlled, adaptive phase IIb trial to assess vafidemstat’s efficacy in treating borderline personality disorder”. PORTICO (EudraCT 2020-003469-20, NCT04932291) was a global double-blind, randomized, placebo-controlled, adaptive 14-week Phase IIb trial evaluating the efficacy and safety of vafidemstat in a BPD population. The trial had two primary endpoints: reduction of agitation and aggression and overall disease improvement in BPD severity. The trial also included two secondary endpoints also exploring the reduction of agitation and aggression and overall disease improvement in BPD severity by different scales. The trial opened a total of 27 clinical sites, 14 in the U.S. and 13 in Europe (Germany, Spain, Bulgaria, and Serbia), and recruited a total of 210 patients, randomized 1:1 in two arms. In January the company released PORTICO topline data showing that, although the primary endpoints, overall improvement by the Borderline Personality Disorder Checklist (BPDCL) and improvement in agitation/aggression by the Clinical Global Impression – Severity Agitation/Aggression (CGI-S A/A), had not reached statistical significance, there was a remarkable nominal statistical significance on two secondary endpoints: overall improvement of the disease measured by the Borderline Evaluation of Severity (BEST) at weeks 8-12 (p = 0.042), and also on the reduction of agitation/aggression measured by the State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger at weeks 8-12 (p = 0.026). Vafidemstat was safe and well tolerated, consistent with the overall safety profile to date. The final analysis of the data has resulted in a clear improvement in most of the measures released in January. Following this oral presentation at ECNP, the results will be subsequently published in a peer-reviewed medical journal. The company has requested the FDA an End-Of-Phase 2 meeting to discuss the design of a registrational Phase III trial with vafidemstat in BPD. Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6, where ORY-4001 has been nominated as clinical candidate for the treatment of certain neurological disorders such as CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com 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, finalized and with published topline data. Based on PORTICO’s results, the company has requested 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. Borderline Personality Disorder (BPD) is one of the most complex, functionally debilitating and costly psychiatric illnesses for healthcare systems, affecting between 0.5 and 1.6% of the general population. BPD patients often experience emotional instability, impulsivity, irrational beliefs and distorted perception, and intense but unstable relationships with others. Up to 10% of those affected die by suicide. Psychotherapy is the first-line treatment and while medications may be prescribed to treat specific symptoms, there is no FDA-approved treatment for BPD patients. It is estimated that around 1.4 million BPD patients in the U.S. are being treated with off-label drugs, approved for other conditions and which manage symptoms rather than the disease itself. The content above comes from the network. if any infringement, please contact us to modify.

Data from the first two cohorts demonstrated that combination of iadademstat plus gilteritinib was safe and showed strong antileukemic activityA third cohort is ongoing following FDA’s OPTIMUS guidance MADRID and CAMBRIDGE, Mass., June 14, 2024 (GLOBE NEWSWIRE) -- 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 presents preliminary data from its ongoing Phase Ib FRIDA study investigating iadademstat in combination with gilteritinib in relapsed/refractory acute myeloid leukemia (AML) patients harboring a FMS-like tyrosine kinase mutation (FLT3 mut+) at the European Hematology Association (EHA) 2024 congress, being held in Madrid (Spain) on June 13–16. Dr. Amir Fathi, from the Massachusetts General Hospital and Principal Investigator of the study, will present a poster communication entitled “Preliminary results of the FRIDA study: iadademstat and gilteritinib in FLT3-mutated R/R AML”. Dr. Carlos Buesa, Oryzon’s CEO, stated, “We are very excited with these preliminary results, which showed in a mostly refractory patient population a higher-than-expected antileukemic activity in the first two cohorts. We, and others, have previously described the strong synergism of the combination of iadademstat with gilteritinib, and these clinical data confirm this synergism. The observed LSD1 full occupancy data in the first two cohorts outlines that we need to reduce the dose to optimize the marrow recovery and achieve a higher degree of complete responses. With the capability to quantify the levels of LSD1 occupancy, we are in an optimal situation to follow the FDA’s OPTIMUS guidance. The safety profile is so far adequate as expected and recruitment continues.” Summary of the main results reported at EHA-2024 The combination of iadademstat and gilteritinib appears safe and well-tolerated, with no dose limiting toxicities (DLTs) reported in the 28-day DLT evaluation period in the first two cohorts: initial cohort (n=6, iadademstat 100 μg) and DL-1 cohort (n=7, iadademstat 75 μg). There were no unexpected Treatment Emergent Adverse Events (TEAEs).Encouraging antileukemic activity observed, with 9 out of 13 patients (69%) achieving bone marrow (BM) blast clearance in the first cycle. Five out of 13 patients (38%) achieved complete remission (CR), complete remission with partial hematological recovery (CRh) or complete remission with incomplete blood count recovery (CRi). Of note, 11 out of 13 patients were refractory to prior standard regimens including venetoclax, 7+3 and midostaurin. Two patients have undergone hematopoietic stem cell transplantation.Platelet count recovery has been slow in most patients, limiting so far a rapid transition from morphologic leukemia-free state (MLFS) to CR/CRh. Since LSD1 plays a key role in hematopoiesis and both iadademstat doses evaluated in the first two cohorts (starting dose and DL-1) showed full LSD1 target engagement (≈90%), lower doses are being investigated with the aim of maintaining efficacy and improving platelet recovery, in accordance with the FDA’s Optimus Project requiring to identify the minimum safe and biologically active dose.FRIDA is currently accruing patients to the third cohort, DL-2 (iadademstat 75 μg, 3 weeks treatment per cycle). Two patients have been enrolled, with no reported DLTs to date.Pharmacokinetic (PK) data support there is no drug-drug interaction between iadademstat and gilteritinib. FRIDA (NCT05546580) is an escalation/expansion, open-label, single arm, multicenter Phase Ib trial to establish the safety, tolerability, and the recommended Phase II dose (RP2D) of the combination of iadademstat with gilteritinib. The study has been designed according to the FDA’s Project Optimus and consists of 2 parts: a dose finding part to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and emerging activity of the combination, and to determine the pharmacologically-active dose (i.e., the minimum safe and biologically active dose) of iadademstat in combination with gilteritinib, and an expansion part at the specific dose(s) selected to evaluate the activity of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML. The trial is conducted in the US and plans to accrue up to approximately 45 patients. Oryzon is further expanding the clinical development of iadademstat in AML through an Investigator-initiated study (IIS) led by Oregon Health & Science University (OHSU). This trial is a Phase Ib dose-finding study to evaluate iadademstat in combination with the SoC, venetoclax and azacitidine, in first line AML patients and is expected to begin enrolling patients in the coming weeks. In addition, in neuroendocrine tumors, in the context of the CRADA agreement between Oryzon and the NIH, the NCI is sponsoring a randomized Phase I/II trial in 1L extensive disease small cell lung cancer combining iadademstat with immune checkpoint inhibitors. The IND for this trial was recently approved by the FDA. A copy of the EHA-2024 poster is available here. About Oryzon Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS and iadademstat in oncology, in several Phase II clinical trials. The company has other pipeline assets directed against other epigenetic targets like HDAC-6, where ORY-4001 has been nominated as clinical candidate for the treatment of certain neurological disorders such as CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com 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 Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and efficacy data in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is being evaluated in a collaborative Phase II basket study with the Fox Chase Cancer Center (FCCC) in combination with paclitaxel in R/R neuroendocrine carcinomas, and the company is preparing a new trial in combination with immune checkpoint inhibitors (ICI) in SCLC. Oryzon has entered into a Cooperative Research and Development Agreement (CRADA) with the U.S. National Cancer Institute (NCI) to collaborate on potential further clinical development of iadademstat in different types of solid and hematological cancers; a first trial in combination with ICI in SCLC has recently received FDA IND approval. In total iadademstat has been dosed so far to more than 130 cancer patients in four clinical trials. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. 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 Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This press release is not an offer of securities for sale in the United States or any other jurisdiction. Oryzon’s securities may not be offered or sold in the United States absent registration or an exemption from registration. Any public offering of Oryzon’s securities to be made in the United States will be made by means of a prospectus that may be obtained from Oryzon or the selling security holder, as applicable, that will contain detailed information about Oryzon and management, as well as financial statements. IR, USIR & Media, EuropeSpainOryzonAshley R. RobinsonSandya von der WeidPatricia Cobo/Mario CorderaEmili TorrellLifeSci Advisors, LLCLifeSci Advisors, LLCAtreviaChief Business Officer+1 617 430 7577+41 78 680 05 38+34 91 564 07 25+34 673 33 97 65+34 93 515 1313arr@lifesciadvisors.comsvonderweid@lifesciadvisors.compcobo@atrevia.commcordera@atrevia.cometorrell@oryzon.com