Respiratory Distress Syndrome

Like most health systems across the United States, Pinehurst, North Carolina-based FirstHealth of the Carolinas has challenges with bed capacity and is always working on new and innovative ways to increase it in a safe and financially responsible way. THE PROBLEM This has been done through a few different venues. FirstHealth's extended care unit at its Richmond campus, among others, is a brick-and-mortar solution, whereas the observation at home (OAH) program helps with capacity challenges, but virtually. PROPOSAL The OAH program is designed to help increase bed capacity across the health system by discharging stable patients who can be managed at home via the program but would otherwise need to have stayed in the hospital if taken care of by traditional medicine. OAH offers multiple entities in the health system an alternative for some of the more stable patients occupying a bed. Once patients are referred to the program, a paramedic will visit them in their home the next day – exceptions are referrals from home health , which I will explain in a moment – where they will perform an in-person assessment that includes vital signs. Once the assessment is complete, the paramedic connects to a provider to complete the remainder of the visit via secure tele-video. FirstHealth uses Epic for these sessions. While the paramedic is present in the patient's home, the provider assesses the patient by tele-video and includes input from the paramedic to continue the patient's care. During the visit, the provider can order medications or labs. Of note, the paramedics do not use an ambulance for this program. The provider also will determine if the patient should be seen again, or if they are stable enough to be discharged from the program. The purpose of the OAH program is to help patients get over the acute phase of their illness. The average length of stay in the program is just over three days. After being released from the OAH program, patients already enrolled in home health will continue those visits. If the patient is not enrolled in home health, they will be transitioned to the virtual care at home program (VCAH). This program uses remote patient monitoring using devices from Health Recovery Solutions so staff can follow the patient's vital signs for the next few days and up to a couple of weeks. Patients also have access to a registered nurse via telephone if needed while in the VCAH. The VCAH program is provided at no cost to the patient and is part of a larger effort to help manage bed capacity. Staff see patients with the following diagnoses but can evaluate others on a case-by-case basis: CHF, COPD, pneumonia, influenza, COVID19, asthma, need for IV antibiotics, cellulitis rechecks and abdominal pain rechecks. Patients can be referred to OAH in a variety of manners: Inpatient referrals. Stable patients are referred to OAH by the hospitalist team. These are patients who remain stable and are enrolled into the OAH program to continue the remaining few days of care that would traditionally have been completed in a hospital bed. Emergency department referrals. Stable patients who would have traditionally been admitted to an in-hospital observation unit for a variety of reasons can now be discharged into the OAH program. Home health. Patients enrolled in home health who may have an acute issue arise. These are stable patients, but who normally would have been referred to the ED for further workup or treatment. Approximately 80% of patients sent to the ED by home health are admitted for observation. OAH is now an option for home health for their stable patients to be seen instead of having to send them to the ED. Patients with potential dangerous cardiac, pulmonary, neurological or other potentially unstable complaints are still sent to the ED immediately via 911. Patients typically seen in OAH from referrals by home health tend to be early onset COPD exacerbation, patients with CHF who have weight gain or increased shortness of breath but are not in respiratory distress, or patients with an upper respiratory infection who need further evaluation. For these patients, staff can intervene at an early stage of an exacerbation and help to keep the patient from needing to go to the ED. Patients referred to OAH are typically seen the same day as the referral. Primary care providers or convenient care providers. PCP or convenient care providers can also refer patients to OAH, where they are seen the next day, and assure their plan of care is effective and the patient is improving, but also to continue to provide care they may not have otherwise received unless being sent to the ER. The main referrals staff see from PCP and convenient care are COPD exacerbations and acute respiratory infections such as COVID-19, influenza or pneumonia in at-risk populations. MEETING THE CHALLENGE "We complete our telemedicine video visits using the Epic EHR," said Stephen Kapa, administrative director of telehealth services at FirstHealth of the Carolinas. "All information is relayed through that platform. For the patients who transition to the VCAH program, we use Health Recovery Solutions blood pressure cuffs and pulse oximeters. The patients download an app from the vendor on their phone and can upload their readings from their monitoring devices through the app. "A nurse monitors those daily and calls patients directly if someone has vital signs out of range," he continued. "Patients can also call the nurse directly with any concerns. Occasionally, we need to initiate a tele-video visit where patients are either re-enrolled into the OAH program or advised to go to the ED." FirstHealth has found keeping things as simple as possible is the best strategy, and that has worked since the COVID-19 pandemic. Too often, the more complicated things are made, the clunkier they become, resulting in more steps that are less likely to be used – keep things simple, Kapa added. RESULTS "One of our biggest achievements in the past 14 months has to be the average daily census in the program," Kapa reported. "Our fiscal year runs from October to October. In the first week of October of 2023, our average daily census was under two. We have had our peaks and troughs over the year, but the trend line has always been positive. In the last week of our fiscal year, we averaged 13 patients per day. "This has had a significant impact contributing to increased patient access and bed capacity as well as increased patient satisfaction and employee engagement," he continued. "We expect the average daily census to continue to climb, especially with the normal increase in volume of patients during the winter months." Another success that staff are quite happy with is their 30-day readmission rate for heart failure and for all-causes. "The average national 30-day readmission rate for heart failure and all-cause readmissions is approximately 20% and 14.5%, respectively," Kapa noted. "For patients admitted to the OAH program, the percentage for both heart failure and all-cause readmissions is under 10%. While this does represent a cost savings, more importantly it shows we can safely and effectively take care of patients with the OAH program. "Lastly, a subjective measure we really can't keep track of is the appreciation of patients and family who are thankful to receive their care safely at home instead of having to be admitted to the hospital," he added. "We have had so many words of thanks and gratitude for what this program has done to help them be where they are most comfortable – at home." ADVICE FOR OTHERS "My advice is twofold," Kapa said. "Keep things as simple as possible and be persistent. As you can see by the growth of our average daily census, it didn't grow overnight nor on its own. You need to be very persistent in delivering your message about the program to all groups, especially providers and discharge planners. "From a provider's perspective, many have been practicing medicine for some time," he continued. "They are used to doing things in a regimented and traditional fashion. I'm a physician assistant by training, so I understand this. Giving them the option of the OAH program gives them another option that hasn't traditionally been there. All you need is to be persistent and share the success stories. Share the data, as sparse as it may be in the beginning." And go to all of the provider meetings possible, he added. "Go to the discharge planner meetings, go to interdisciplinary rounds, speak about the program anywhere you can," he concluded. "Once the providers start to see the benefits of the program, see that their patients are being taken care of safely and see the readmission rates dropping, this will take on a life of its own. I'm hoping we are in this latter stage now." Follow Bill's HIT coverage on LinkedIn: Bill Siwicki Email him: bsiwicki@himss.org Healthcare IT News is a HIMSS Media publication.

Final data from PORTICO, global Phase IIb vafidemstat trial in BPD, presented at the 37th ECNP annual conference in September Company moving forward with PORTICO-2 Phase III trial preparations following positive feedback from End-of-Phase II meeting with the FDA Company continues to strengthen IP position for vafidemstat with additional “intention to grant” communications First cohort dosed in Investigator-initiated Phase Ib study of iadademstat with venetoclax and azacitidine in first-line AML Reduction in R&D expenses for the nine months ended September 30, 2024 as a result of completion of the PORTICO clinical trial; savings of $5.1M with respect to the nine months ended September 30, 2023 MADRID and CAMBRIDGE, Mass., Oct. 24, 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 reported financial results for the nine months ending September 30, 2024 and provided a corporate update on recent developments. Dr Carlos Buesa, Oryzon’s Chief Executive Officer said, “This quarter marked a pivotal moment for our CNS program. At the ECNP 2024 Conference, we presented the full dataset from our Phase IIb PORTICO trial of vafidemstat for Borderline Personality Disorder (BPD), and we observed notable improvements across most study endpoints compared to the topline data released in January. We also received the official minutes from our End-of-Phase II meeting with the FDA, confirming that we can proceed to a Phase III. The FDA indicated that agitation/aggression in BPD may be an acceptable indication, and agreed that we may use the same aggression scale that showed the strongest signal in Phase II. With this positive feedback, we will now begin preparations to submit the full Phase III protocol to the FDA. Careful analysis of the effect sizes in BPD has allowed us to reevaluate and increase the recruitment target for the EVOLUTION trial in schizophrenia, which continues to enroll patients in Spain. Meanwhile, we have strengthened our CNS intellectual property portfolio with additional “intention to grant” communications in two key patent families covering the use of vafidemstat in treating aggression, social withdrawal and BPD. These advancements significantly bolster our IP position for vafidemstat.” Dr Buesa continued, “In oncology, following the very positive results of our ALICE trial with iadademstat in first-line unfit AML patients, we are expanding our efforts to further evaluate therapeutic efficacy in this patient population through two additional trials. One is conducted under our CRADA agreement with the NCI, while the other is in collaboration with Oregon Health & Science University (OHSU) as an investigator-initiated study (IIS). Both trials will assess iadademstat in combination with azacitidine and venetoclax in first-line AML. The OHSU-led IIS trial has already enrolled the first cohort, representing a significant advancement in our oncology program and, if positive, could open additional options for our clinical development strategy. In addition, a new IIS sponsored by the Medical College Wisconsin in combination with azacitidine in patients with myelodysplastic syndrome is being prepared. In June, we presented promising initial data from our ongoing FRIDA Phase Ib trial, evaluating iadademstat in combination with gilteritinib in relapsed/refractory FLT3-mutant AML patients, at the EHA Conference. The data from the first two cohorts demonstrated that the combination was safe and showed strong antileukemic activity, with encouraging response rates and a shorter time to response compared to historical data on gilteritinib alone. We have since completed enrollment of the third cohort, and as the data matures, we plan to present additional results at the EHA Conference next June.” Dr Buesa added, “The positive outcome of the End-of-Phase II meeting with the FDA has been a turning point for the company, as it transitions into a Phase III company for the first time. While we remain committed to maintaining strict budgetary discipline and leveraging access to our Convertible Notes program, we anticipate receiving further financial support from the recently approved IPCEI grant from the EU, which will provide crucial resources to advance our R&D in personalized medicine for both CNS and oncology. The company is also actively engaged in discussions with corporate partners to explore potential partnerships and will continue evaluating additional financing opportunities.” Third Quarter and Recent Highlights Vafidemstat in large multifactorial CNS indications: Final data from vafidemstat’s Phase IIb PORTICO trial in BPD were presented at the New Medications Symposium, a special symposium focused on clinical trials of new compounds within the 37th European College of Neuropsychopharmacology (ECNP-2024) congress held in September in Milan, Italy. A strong improvement in State-Trait Anger Expression Inventory 2 (STAXI-2) Trait Anger, a measure of agitation and aggression, at Weeks 8–12 was observed compared to previous top line data (TLD); nominal statistical significance now of p = 0.0071 (previously 0.0259). An improvement in Borderline Evaluation of Severity (BEST), an overall measure of BPD disease severity, at Weeks 8–12 compared to TLD was also achieved; nominal statistical significance now of p = 0.0260 (previously 0.0423). Vafidemstat showed favorable results over placebo in all primary and secondary efficacy endpoints, as demonstrated by T-Forest plot analysis. The final analysis confirmed now a global treatment effect favoring vafidemstat by the Global Statistical Test (GST), with the GST p-value showing a statistical significance, particularly when considering global improvement in the severity of the disease and in agitation/aggression (p = 0.0362). Vafidemstat was, as in all previous clinical studies, safe and well-tolerated. Oryzon has received the minutes from the end-of-Phase II meeting with the U.S. Food and Drug Administration (FDA). Based on the positive feedback received, ORYZON has started preparations for Phase III, including the preparation of a full protocol for the PORTICO-2 Phase III trial to submit to the FDA for study approval. The trial will use STAXI-2 Trait anger as a primary efficacy endpoint measure. Secondary endpoints will include both patient-rated and clinician-rated scales, such as CGI-S A/A to assess agitation/aggression, and BEST and CGI-S to assess overall BPD improvement.The estimated total sample size for PORTICO-2 is 350 patients (randomized 1:1 vafidemstat or control), with a trial duration of 18 weeks in total. Subject to FDA’s review of the final data, the PORTICO-2 Phase III study has the potential to be one of the two registrational trials required by the FDA. The company expects to obtain FDA’s approval for PORTICO-2 by end of 1Q2025. Oryzon has continued to strengthen its patent portfolio for vafidemstat during this quarter. The European Patent Office (EPO) recently granted Oryzon’s European patent EP3661510B1, titled “Methods of treating behavior alterations”; the granted claims cover the use of vafidemstat for the treatment of aggression and social withdrawal. A corresponding patent has also been granted in South Korea and we have received “intention to grant” communications in Australia and Malaysia. These patents will not expire until at least 2038, excluding any potential patent term extension that may provide additional years of protection. In addition, Oryzon has received “intention to grant” communications in Europe and Mexico for another key patent family related to vafidemstat titled “Methods of treating borderline personality disorder”, and a corresponding patent has been granted in Japan. These patents will not expire until at least 2040, excluding potential patent term extensions that may provide additional protection. Another patent, covering the use of vafidemstat to treat ADHD, has also been granted in Japan during this period. The EVOLUTION Phase IIb clinical trial evaluating vafidemstat in patients with schizophrenia continues to enroll participants. This study aims to assess the efficacy of vafidemstat, with a primary focus on improving negative symptoms. Following a careful analysis of effect sizes observed in BPD, we have reevaluated and increased the recruitment target for the trial. In addition to negative symptoms, the trial is also exploring as secondary endpoints vafidemstat’s efficacy in improving cognitive impairment and positive symptoms in schizophrenia. The project is partially funded by the Spanish Ministry of Science and Innovation and is being conducted at multiple hospitals across Spain. Vafidemstat in monogenic CNS indications: We continue to evaluate the feasibility of a new precision medicine trial in Kabuki Syndrome. The company will decide on a possible submission of an IND for HOPE to the FDA in 2025. 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. Following the FDA’s new OPTIMUS doctrine, the company continues to explore the minimal dose with clinical activity. 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 first patients have been dosed in the Investigator-initiated study (IIS) sponsored by the Oregon Health & Science University (OHSU) Knight Cancer Institute evaluating the combination of iadademstat with venetoclax and azacitidine in first line AML. Dr. Curtis Lachowiez is the Principal Investigator (PI) of the trial. This Phase Ib dose-finding study is now actively enrolling patients. Iadademstat will also be evaluated in combination with venetoclax and azacitidine in first-line AML patients in a trial under the Cooperative Research and Development Agreement (CRADA) signed with the National Cancer Institute (NCI) in the United States. The trial will be conducted and sponsored by the NCI, with Dr. Natalie Galanina from the University of Pittsburgh Cancer Institute as the main PI for the trial. The trial plans to enroll 45 patients and, according to NCI, is expected to start enrolling patients in 4Q2024. The Company is further expanding the clinical development of iadademstat in hemato-oncology through a new IIS led by the Medical College of Wisconsin, which will evaluate iadademstat in combination with azacitidine in adult subjects with myelodysplastic syndrome. 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 Fox Chase Cancer Center. The Phase I/II trial with iadademstat plus immune checkpoint inhibitors in first line SCLC patients with extensive disease under the CRADA agreement with the NCI, already approved by the FDA, is now ready to start enrolling patients. The trial is titled “A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer” and will be conducted and sponsored by the NCI, with Dr. Charles Rudin from the Memorial Sloan Kettering Cancer Center (MSKCC) as the main PI for the trial, and Dr. Noura Choudhury from University of Chicago as co-PI A number of prestigious cancer centers in the US, including the MSKCC, the JHU Sidney Kimmel Comprehensive Cancer Center and many others will participate. The trial plans to enroll 45-50 patients and is expected to start enrolling patients in 4Q2024. The STELLAR trial, a randomized, multicenter Phase 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. 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, continues to progress through IND enabling studies to prepare it for clinical studies. Financial Update: Third quarter 2024 Financial Results Research and development (R&D) expenses were $1.9 million and $7.1 million for the quarter and nine months ended September 30, 2024, compared to $3.8 and $12.2 million for the quarter and nine months ended September 30, 2023. As a result of the completion of the PORTICO clinical trial, the company saves $5.1M with respect to the third quarter of 2023. General and administrative expenses were $0.9 and $3.1 million for the quarter and nine months ended September 30, 2024, compared to $0.7 and $2.9 million for the quarter and nine months ended September 30, 2023. Net losses were $1.1 and $3.8 million for the quarter and nine months ended September 30, 2024, compared to $0.8 and 3.4 million for the quarter and nine months ended September 30, 2023. 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 $2.5 million (–$0.04 per share) for the nine months ended September30, 2024, compared to a negative net result of $1.7 million (–$0.03 per share) for the nine months ended September 30, 2023. Cash, cash equivalents, and marketable securities totaled $8.4 million as of September 30, 2024. ORYZON GENOMICS, S.A. BALANCE SHEET DATA (UNAUDITED) 1 (Amounts in thousands US $) September 30th, 2024 September 30th, 2023 Cash and cash equivalents 8,442 8,818 Marketable securities 0 0 Total Assets 122,661 108,303 Deferred revenue 0 0 Total Stockholders’ equity 96,854 83,920 ORYZON GENOMICS, S.A. STATEMENTS OF OPERATIONS (UNAUDITED) 1 (US $, amounts in thousands except per share data) Three Months Ended September 30th Nine Months Ended September 30th 2024 2023 2024 2023 Collaboration Revenue 0 0 0 0 Operating expenses: Research and Development 1,915 3,821 7,076 12,237 General and administrative 879 674 3,051 2,934 Total operating expenses 2,794 4,495 10,127 15,171 Loss from Operations -2,794 -4,495 -10,127 -15,171 Other income, net 1,671 3,669 6,312 11,728 Net Loss -1,123 -826 -3,815 -3,443 Net Financial & Tax -256 -300 1,272 1,716 Net Result -1,379 -1,126 -2,543 -1,727 Loss per share allocable to common stockholders: Basic -0.02 -0.02 -0.04 -0.03 Weighted average Shares outstanding Basic 63,383,939 58,154,298 62,336,626 57,234,937 1 Spanish GAAP 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 . 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 & 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, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU. 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; the first two trials will evaluate iadademstat in combination with ICI in SCLC and in combination with azacitidine and venetoclax in 1L AML. Oryzon is further expanding the clinical development of iadademstat through additional investigator-initiated studies. Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. 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 negative symptoms of schizophrenia, named EVOLUTION (recruitment ongoing), and another one in Borderline Personality disorder (BPD), named PORTICO, completed and with published final data. Following receipt of the minutes from the End-of-Phase II meeting with the FDA to discuss PORTICO’s results, the company recently announced plans to move forward with a Phase III PORTICO-2 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 evaluating 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 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

LA JOLLA, Calif., Oct. 23, 2024 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced the lead Principal Investigator of this clinical trial, Björn Oskarsson, MD, FAAN presented the update of an ongoing Phase 2/3 clinical trial of MN-166 (ibudilast) in Amyotrophic Lateral Sclerosis (ALS) patients at the 2024 Annual NEALS Meeting being held virtually on Oct 21-24, 2024. The presentation entitled “COMBAT-ALS Phase 2b/3 Trial of MN-166 (Ibudilast) in ALS: Study Design and Trial Update” was given by Dr. Oskarsson during the poster session. Dr. Oskarsson discussed the background of MN-166 (ibudilast), scientific rationale, study objectives, study design, major inclusion criteria and enrollment update as of October 18, 2024. Additionally, he discussed the new NIH funding Expand Access Protocol clinical trial*1 in ALS patients. *1:https://investors.medicinova.com/news-releases/news-release-details/medicinova-support-nih-funded-expanded-access-clinical-trial About MN-166 (ibudilast) MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS). About MediciNova MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety profiles, MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in Long COVID and substance dependence. MN 001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants. Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-001, MN-221, and MN-029. These forward-looking statements may be preceded by, followed by, or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," “considering,” “planning” or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-001, MN-221, and MN-029 and risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, the availability of funds to complete product development plans and MediciNova's ability to obtain third party funding for programs and raise sufficient capital when needed, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2023 and its subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements. INVESTOR CONTACT: David H. Crean, Ph.D.Chief Business OfficerMediciNova, Incinfo@medicinova.com