OHSU Knight Cancer Institute

Exploring the triple combination with venetoclax and azacitidineStudy sponsored by Oregon Health & Science University (OHSU) MADRID and CAMBRIDGE, Mass., Sept. 09, 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, announced today that the first patient has been dosed in an investigator-initiated Phase Ib dose-finding trial of iadademstat, Oryzon’s potent and selective LSD1 inhibitor, in combination with venetoclax and azacitidine in newly diagnosed acute myeloid leukemia (AML), sponsored by the Oregon Health & Science University (OHSU) Knight Cancer Institute. Under the direction of Dr. Curtis Lachowiez at OHSU Knight Cancer Institute, the study (NCT06357182) aims to test the safety, tolerability, and best dose of iadademstat when administered together with the standard-of-care venetoclax and azacitidine in treating patients with newly diagnosed AML. The trial also aims to assess the preliminary efficacy of the triple combination. Dr. Curtis Lachowiez, Principal Investigator of the study, stated: “Given the activity observed with LSD1 inhibition in combination with azacitidine in AML, testing a triplet combination including iadademstat with the highly active backbone of azacitidine+venetoclax is the logical next step to hopefully improve outcomes of patients living with AML if proven to be safe and active”. Dr. Carlos Buesa, Oryzon’s CEO, added: “This trial builds on the positive results obtained in our ALICE trial in first-line AML, where the combination of iadademstat with azacitidine showed strong antileukemic activity with deep and durable responses and a manageable safety profile, including in patients with high-risk prognostic factors that respond poorly to venetoclax+azaciditine.” In AML, iadademstat is also being evaluated in a company-sponsored Phase Ib trial in combination with gilteritinib in patients with relapsed/refractory AML harboring a FMS-like tyrosine kinase mutation (FLT3mut+). This FRIDA trial is being conducted in the U.S. Preliminary results from FRIDA, corresponding to the first two cohorts, were recently presented at the European Hematology Association (EHA) 2024 congress in June. Our results demonstrated that combination of iadademstat plus gilteritinib was safe and well tolerated, and showed encouraging antileukemic activity. 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 a clinical candidate ORY-4001, has been nominated for its possible development in 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 IadademstatIadademstat (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 & The Lancet Haematology, 2024, 11(7):e487-e498). 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. Oryzon is further expanding the clinical development of iadademstat through investigator-initiated studies. 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. Spain Oryzon IR, US IR & Media, Europe Patricia Cobo/Mario Cordera Emili Torrell Ashley R. Robinson Sandya von der Weid Atrevia Chief Business Officer LifeSci Advisors, LLC LifeSci Advisors, LLC +34 91 564 07 25 +34 673 33 97 65 +34 93 515 1313 +1 617 430 7577 +41 78 680 05 38 pcobo@atrevia.com mcordera@atrevia.com etorrell@oryzon.com arr@lifesciadvisors.com svonderweid@lifesciadvisors.com

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Electra Therapeutics, Inc., a clinical stage biotechnology company developing antibody therapies against novel targets for a broad range of immunological diseases and cancer, announced today the appointment of Graham Parry, PhD, as Chief Scientific Officer and Kim-Hien Dao, DO, PhD, as Chief Medical Officer. Both executives have deep experience in drug development and each have been instrumental in leading multiple drug candidates through clinical trials and toward regulatory approval. “We are delighted to have such exceptional leaders as Graham and Kim-Hien join our management team at a time of great momentum for the company, with clinical proof-of-concept established for our lead candidate, ELA026,” said Kathy Dong, PharmD, MBA, President and Chief Executive Officer of Electra Therapeutics. “Graham’s scientific leadership across our cross-functional teams will be highly valued as we maximize the potential of ELA026 and pursue a broad range of opportunities to address unmet needs in immune-mediated diseases and cancer. Kim-Hien has demonstrated outstanding clinical and translational research expertise that will be instrumental in guiding ELA026 through the clinic as a first-in-class antibody therapy for patients with sHLH, a severe inflammatory disease with critical unmet needs and no approved treatment.” Dr. Parry stated, “I am enthusiastic about Electra’s approach to combining rigorous research and novel biology to deliver new therapies to under-served patient populations. The opportunity to work alongside this outstanding team with such a clear and focused mission is truly a privilege.” Dr. Graham Parry brings over 20 years of experience to the development of novel therapies for rare and life-threatening diseases. Prior to joining Electra, he served as Executive Vice President of Translational Sciences at Star Therapeutics where he worked across a range of R&D programs to advance the development of novel treatments for multiple diseases. Previously, he served as Senior Vice President of Translational Sciences at Third Harmonic Bio, focused on treatments for allergic and inflammatory diseases, and as Vice President of Technical Operations at True North Therapeutics where he worked on the discovery and development of ENJAYMO®, a first-in-class inhibitor of the classical complement pathway approved for the treatment of cold agglutinin disease. Earlier in his career, he worked in drug development roles at iPierian in neurodegenerative diseases and Attenuon in cancer therapeutics, and as an assistant professor at The Scripps Research Institute. Dr. Parry earned his BSc at Brunel University and his PhD at the University of London. Dr. Dao commented, "I am delighted to take on this role during such an exciting time at Electra as the company advances ELA026 as a promising new therapy for patients with sHLH who currently lack effective treatment options. I look forward to the work ahead to build on the encouraging data to date for ELA026 in sHLH as well as in additional indications, and to contribute to the company’s continued progress.” Dr. Kim-Hien Dao is a clinician scientist with more than 15 years of clinical and translational research experience in academia and biotech. She joined Electra in April 2023 as Vice President, Head of Clinical Development. Prior to joining Electra, she was Executive Medical Director at Astex Pharmaceuticals, where she worked on four drug programs for solid tumors and hematological malignancies. Previously, she had an 11-year tenure at Oregon Health and Science University (OHSU) and had a clinical focus in myelodysplastic syndromes, myeloproliferative neoplasms, bone marrow failure syndromes, bone marrow transplant, and clonal hematopoiesis. She also ran a research laboratory that was funded by the National Institutes of Health and the OHSU Knight Cancer Institute. Dr. Dao received her DO, PhD from Michigan State University and trained in Hematology-Medical Oncology at the University of California at San Diego. She is an actively practicing hematologist-oncologist in a volunteer capacity. About Electra Therapeutics Electra Therapeutics is a clinical stage biotechnology company developing therapies against novel targets for a broad range of immunological diseases and cancer. The company’s lead product candidate, ELA026, is a monoclonal antibody that targets SIRP on the cell surface of myeloid cells and T lymphocytes, and precisely depletes pathological immune cells. ELA026 is in clinical development for secondary hemophagocytic lymphohistiocytosis (sHLH), a rare, life-threatening hyperinflammatory condition for which there is no approved treatment, as well as additional disease indications. For more information, please visit and follow us on LinkedIn. View source version on businesswire.com: Contacts Media: Kathryn Morris The Yates Network 914-204-6412 kathryn@theyatesnetwork.com Source: Electra Therapeutics View this news release online at:

People with the heart condition obstructive cardiomyopathy were able to use significantly more oxygen while exercising after taking the investigational drug aficamten, according to a new study. People with a common heart condition were able to use significantly more oxygen while exercising after taking an investigational drug in an international clinical trial, according to a study published today in the New England Journal of Medicine. The finding wasalso presented today at the European Society of Cardiology's Heart Failure 2024 meeting in Lisbon, Portugal. Oregon Health & Science University is part of the randomized, double-blind Phase 3 trial that is evaluating the experimental drug aficamten, which was developed by Cytokinetics to treat the obstructive form of hypertrophic cardiomyopathy, or HCM. Of the 282 adults participating in the trial, 19 enrolled through OHSU -- the most of any trial center. "By having more oxygen available during exercise, patients with obstructive hypertrophic cardiomyopathy can more easily walk, perform household chores, and do other everyday tasks," said cardiologist Ahmad Masri, M.D., M.S., who co-wrote today's paper and directs the OHSU Knight Cardiovascular Institute's Hypertrophic Cardiomyopathy Center. "Our latest clinical trial results suggest aficamten is a promising treatment for HCM." HCM affects about 1 in 500 people and is one of the most common causes of sudden death for youth and otherwise healthy athletes. Often caused by inherited gene mutations, it thickens heart muscles and makes it difficult for the heart to work as it should. It causes shortness of breath and reduces people's ability to exercise. The obstructive form of HCM reduces blood flow out of the heart. About half of the trial's participants were given the experimental drug, and the other half took a placebo and served as the study's control group. Scientists measured the participants' oxygen levels while they used treadmills or bicycles. Those who took aficamten had a significant increase in their maximum oxygen use -- 1.7 milliliters per kilogram per minute more than those in the control group. Having an increased peak oxygen uptake can improve a patient's ability to be physically active, whereas reduced oxygen uptake can increase the risk of experiencing heart failure, needing a heart transplant, and dying. Non-drug treatment options for obstructive HCM include surgery to remove excess heart muscle. In 2022, the Food and Drug Administration also approved mavacamten as the first drug designed to target the underlying cause of obstructive HCM. However, mavacamten may increase the risk of heart failure and it interacts with several commonly used medications. As a result, patients who use mavacamten must also undergo intense monitoring. During the past decade, OHSU has been involved in many research studies exploring new HCM treatment options. It has been a center for several mavacamten studies and is participating in gene therapy research. The university is also currently involved in four other aficamten trials that are evaluating it as a potential treatment for various forms of HCM and in different types of patients, including children. "This is an exciting time for treating HCM," Masri said. "While we continue to offer traditional surgical and procedural therapies for HCM, we are now also able to offer patients other treatment options: therapies that were recently approved by the FDA and investigational therapies that are available by participating in clinical trials."