Muscle Spasticity

SL-1002 demonstrated a favorable safety profile in adult patients with limb spasticity, achieving the primary safety endpoint of this first-in-human study. Key secondary efficacy endpoints were also met, including a statistically significant reduction in the Modified Ashworth Score at 6 months. ROSWELL, Ga. and DUBLIN and HAMILTON, Bermuda, Oct. 30, 2024 /PRNewswire/ -- Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, today announced positive topline results from its SL-1002 RAISE Limb Spasticity Trial (NCT05311215). The data were recently presented at the Spasticity X Symposium in Houston, Texas. Dr. Sheng Li, MD, PhD, Professor in the Department of Physical Medicine and Rehabilitation (PM&R) at McGovern Medical School at UTHealth Houston and Director of Stroke Rehabilitation and Recovery Research at TIRR Memorial Hermann Hospital, along with Dr. Gerard Francisco, MD, professor and The Wulfe Family Chair of Physical Medicine and Rehabilitation at McGovern Medical School at UTHealth Houston and Chief Medical Officer at TIRR Memorial Hermann, presented the findings. SL-1002 is a novel chemoneurolytic injection utilizing Saol's proprietary CYCLOPHLEX™ technology. In the RAISE Limb Spasticity Trial, patients were randomized (3:1) into a double-blind, vehicle-controlled, single-ascending-dose escalation study designed to assess the safety and efficacy of a single SL-1002 treatment in patients with mild to severe limb spasticity. The study period lasted 26 weeks post-randomization, and the primary endpoint was to evaluate the overall safety profile of SL-1002 compared to vehicle. A total of 32 patients were randomized in the trial (24 receiving SL-1002, 8 receiving vehicle). Five serious adverse events (SAEs) were reported, all determined by investigators to be unrelated to the treatment. Fourteen non-serious treatment-emergent adverse events (TEAEs) determined by the investigators to be possibly, probably, or definitely related to treatment were observed, all were considered mild. There were other mild and moderate non-serious treatment-emergent adverse events (TEAEs) considered by the investigators to be unrelated to the treatment. Overall, SL-1002 was deemed well-tolerated, with no therapy- or program-limiting adverse events. Key secondary endpoints included assessments using the Modified Ashworth Scale (MAS), the most widely used efficacy measurement in spasticity trials. Despite the trial not being powered for efficacy, SL-1002 demonstrated a statistically significant improvement over vehicle at multiple time points throughout the trial. At 6 months, the SL-1002 arm showed a statistically significant reduction in MAS compared to baseline, with a decrease of -1.18, compared to -0.33 reduction in the vehicle arm (p=0.0060). "We are thrilled to share the positive results from the RAISE Limb Spasticity Trial," said Dave Penake, CEO of Saol Therapeutics. "Spasticity can be an incredibly debilitating condition, and the need for new treatment options has been voiced by patients and clinicians. We are especially encouraged by the strong safety profile observed in the RAISE study, alongside the efficacy shown by SL-1002 lasting at least 6 months. Achieving a 1–2-point reduction in MAS is a significant, positive, clinical outcome, and the durability of the treatment give us great confidence in the future of this program." Penake added, "None of this would have been possible without the patients who volunteered for this study and the dedicated investigators and clinical trial site teams. Their collaboration and commitment are what drive medical progress, and we are deeply grateful for their contributions." Dr. Gerard Francisco, the Principal Investigator for the trial, commented, "Treating spasticity is complex, and there is an urgent need for more innovative therapies. These early results show that SL-1002 appears to be safe, effective, and durable. " The RAISE Limb Spasticity Trial was conducted at UTHealth Houston in Houston, TX, where Dr. Sheng Li and Dr. Gerard Francisco served as the investigators, and at the Medical College of Wisconsin in Milwaukee, WI, where Dr. John McGuire served as the Principal Investigator. Saol Therapeutics plans to meet with the FDA in the first half of 2025 to determine the next steps in the SL-1002 spasticity program. SL-1002 is also being investigated for the treatment of pain related to osteoarthritis of the knee in the COMPASS Osteoarthritis Knee Pain Trial, with results yet to be released. About RAISE Limb Spasticity Trial The RAISE Limb Spasticity trial is a Randomized double-blind, vehicle-controlled, single Ascend Ing dose escalation study to assess the Safety, Pharmacokinetics and Efficacy of SL-1002 in adult patients with limb spasticity. (NCT05311215). About COMPASS Osteoarthritis Knee Pain Trial In addition to the RAISE Spasticity Trial, SL-1002 is also being investigated for the treatment of pain related to osteoarthritis of the knee. The COMPASS Osteoarthritis Knee Pain Trial is a multicenter, randomized, double-blind, vehicle- COntrolled, single-ascending dose escalation study to assess the safety and efficacy of SL-1002 injectable for treat Ment of PAin a SSociated with Osteo Arthritis of the knee. (NCT05470608). About SL-1002 SL-1002 is a novel, chemoneurolytic injection, that utilizes Saol's proprietary CYCLOPHLEX™ technology. It is currently being developed for the treatment of chronic knee pain related to osteoarthritis and limb spasticity, both in the adult population (18+) in the United States. About Saol Therapeutics Saol Therapeutics (pronounced "Sail") is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland, and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit . Saol Therapeutics Contact Senior Vice President, Strategy Brian Nappi [email protected] SOURCE Saol Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Analysis of Cerebral Spinal Fluid (CSF) from patients at pre-treatment baseline to post-treatment intervals up to 24 months demonstrates marked decrease in N-Acetylaspartate (NAA) Magnetic Resonance Imaging (MRI) assessments also show increases in brain white matter and myelin volume as well as functional improvements on validated scales The NAA reduction, MRI assessments and encouraging efficacy and safety data support further development of rAAV-Olig001-ASPA and discussions with regulatory authorities for a potential road map to registration NEW YORK, NY, USA I October 10, 2024 I Myrtelle Inc. (“Myrtelle” or the “Company”), a gene therapy company focused on developing transformative treatments for neurodegenerative diseases, today announced clinical trial findings showing a significant biomarker change in patients treated with the Company’s investigational gene therapy for Canavan disease (CD), rAAV-Oligo001-ASPA. Analysis of Cerebral Spinal Fluid (CSF) from seven patients, observed up to 24-month post treatment milestone revealed that each patient demonstrated a decrease of over 80% in N-Acetylaspartate (NAA) from their baseline measurement. Observations of these patients using Magnetic Resonance Imaging (MRI) also demonstrated increases in brain white matter and myelin volume over the same time intervals. The Company’s open-label Phase 1/2 First-in-Human (FIH) clinical trial is being conducted at Dayton Children’s Hospital (Dayton, Ohio) and includes baseline and post treatment assessments at 1, 3, 6, and 12 months the first year after surgery, and then once every 12 months for 5 years. Myrtelle’s FIH trial utilizes the Company’s proprietary rAAV vector to directly target oligodendrocytes, the brain cells affected in CD which are responsible for producing myelin – the insulating material that enables proper neuronal function. In CD, the production of myelin is impaired due to a mutation in the Aspartoacylase gene ( ASPA) that encodes the enzyme Aspartoacylase (ASPA) which is expressed in the brain solely in oligodendrocytes. The deficiency of ASPA enzyme results in multiple biochemical and anatomic changes, including inability to metabolize N-Acetylaspartate (NAA), a neurochemical that is abundant in the brain and plays an important role in myelin synthesis and brain bioenergetics. Myrtelle’s novel oligodendrocyte-targeting rAAV vector-based gene therapy is intended to restore ASPA function and hence the metabolism of NAA and myelination in patients with CD. Patients have also shown functional improvements on validated functional scales. Observed improvements in these treated patients are in contrast to the continuous clinical deterioration expected with the natural progression of CD. “The combination of changes in NAA levels and myelin volume offers a valuable tool for assessing early therapeutic efficacy in Canavan disease. Improvement in such important disease markers like NAA and myelin, together with functional gains in our patients, is encouraging given the progressive nature of Canavan disease. It drives us to continue our work to bring this potentially important therapy to the patients who currently do not have treatment options,” commented Olga Flamini, Co-CMO at Myrtelle. Myrtelle recently announced that rAAV-Olig001-ASPA was selected by the FDA for participation in the START pilot program in which the gene therapy candidate was one of four CBER-regulated products chosen. rAAV-Olig001-ASPA has also received RMAT, Orphan Drug, Rare Pediatric Disease, and Fast Track designations from the FDA, Orphan Drug Designation & Advanced Therapy Medicinal Product (ATMP) classification from the European Medicines Agency, as well as Innovative Licensing and Access Pathway (ILAP) from the United Kingdom Medicines & Healthcare products Regulatory Agency. ABOUT MYRTELLE Myrtelle Inc. is a gene therapy company focused on developing transformative treatments for neurodegenerative diseases. The company has a proprietary platform, intellectual property, and portfolio of programs and technologies supporting innovative gene therapy approaches for neurodegenerative diseases. Myrtelle has an exclusive worldwide licensing agreement with Pfizer Inc. for its Canavan disease program. For more information, please visit the Company’s website at: www.myrtellegtx.com . ABOUT CANAVAN DISEASE Canavan disease (CD) is a fatal childhood genetic brain disease caused by mutations in the ASPA gene ( ASPA ) which prevent the normal expression of aspartoacylase, a critical enzyme produced in oligodendrocytes. The lack of normal aspartoacylase expression negatively impacts brain bioenergetics and development, including myelin production. Patients with CD are impacted at birth but may appear normal until several months old when symptoms begin to develop. Poor head control, abnormally large head size, difficulty in eye tracking, excessive irritability, severely diminished muscle tone, and delays in reaching motor milestones, such as rolling, sitting, and walking, are the typical initial manifestations of CD. As the disease progresses, seizures, spasticity, difficulties in swallowing, and overall muscle deterioration emerge with most affected children developing life-threatening complications by approximately 10 years of age. Currently, there are no cures for CD, and only palliative treatments are available. More information on Myrtelle’s clinical trial in Canavan disease can be found on https://clinicaltrials.gov/ under the identifier NCT04833907 or by emailing PatientAdvocacy@MyrtelleGTX.com . SOURCE: Myrtelle

ISTANBUL and LONDON, and BOSTON, Oct. 07, 2024 (GLOBE NEWSWIRE) -- Orchard Therapeutics, recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe and Er-Kim, an international pharmaceutical company specializing in the commercialization of novel therapies, today announced the companies have signed an exclusive distribution agreement to commercialize Libmeldy® (atidarsagene autotemcel), the only approved therapy for eligible children with early-onset metachromatic leukodystrophy (MLD). Libmeldy aims to correct the underlying genetic cause of MLD, an ultra-rare, rapidly progressive, irreversible and ultimately fatal neurometabolic disease that affects approximately one in 100,000 live births based on existing literature. Under the agreement, Er-Kim will serve as the exclusive representative of Orchard to identify children eligible for treatment with Libmeldy in international markets across Turkey, Russia, Ukraine, and the Commonwealth of Independent States. Er-Kim will collaborate with Orchard Therapeutics to refer eligible children with early-onset MLD identified in these countries to an established European-based qualified treatment center. “The pharmaceutical and biotech industries have made notable strides in advancing gene therapies and we are thrilled to partner with Orchard Therapeutics to enable access to this important treatment in the region,” said Cem Zorlular, chief executive officer of Er-Kim. “Libmeldy is a potentially transformative therapy for eligible children with early-onset MLD who previously had no approved treatment options beyond supportive and end-of-life care. We are looking forward to working with Orchard and our counterparts in these territories that we specialize in to further implement bespoke approaches to deliver genetic medicines to eligible patients as soon as possible.” “MLD is a devastating disease for which there is evidence of a higher incidence rate in Turkish and Eurasian populations than those in the U.S. and Europe, which heightens our urgency to expand access mechanisms for Libmeldy in these regions,” said Robin Kenselaar, senior vice president and general manager of EMEA at Orchard Therapeutics. “With its extensive regional footprint and deep expertise in delivering specialty medicines to patients in need, we look forward to working with our new partners at Er-Kim to broaden access for eligible children and their families.” About MLDMLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births based on existing literature. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity, and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.i About LibmeldyLibmeldy® (atidarsagene autotemcel) aims to correct the underlying genetic cause of metachromatic leukodystrophy (MLD) by inserting one or more functional copies of the human ARSA gene ex vivo (outside the body) into the genome of a patient’s own hematopoietic stem cells (HSCs) using a lentiviral vector. The genetically repaired cells are infused back into the patient, where, once engrafted, they differentiate into multiple cell types, some of which migrate across the blood-brain barrier into the central nervous system and express the functional enzyme. Prior to treatment, patients must undergo high-dose chemotherapy, a process that removes cells from the bone marrow so they can be replaced with the modified cells in Libmeldy. This approach has the potential to restore enzymatic function to stop or slow disease progression with a single treatment. Libmeldy is approved by the European Commission (EC), UK Medicines and Healthcare products Regulatory Agency (MHRA), and Swiss Agency for Therapeutic Products (Swissmedic). For more information, please see the Summary of Product Characteristics (SmPC) available on the EMA website. The program was originated by and developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. About Er-KimEstablished in 1981, Er-Kim Pharmaceuticals stands at the forefront of biopharmaceutical innovation, partnering with over 40 global leaders to revolutionize patient care in key international markets. Our pioneering business models, tailored for sustainability and flexibility, have positioned us as a full-service solution, extending our reach to over 600 million patients through our fully-owned affiliates. With a dedicated team of over 280 professionals worldwide and revenues exceeding EUR 200M, Er-Kim is not just a partner but a trailblazer in healthcare, continually setting new standards in commercialization and patient access. For more information, please visit http://www.er-kim.com/. About Orchard TherapeuticsOrchard Therapeutics, a Kyowa Kirin company, is a global gene therapy leader focused on ending the devastation caused by genetic and other severe diseases by discovering, developing, and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease with a single treatment. Founded in 2015, Orchard’s roots go back to some of the first research and clinical developments involving HSC gene therapy. Our team has played a central role in the evolution of this technology from a promising scientific idea to a potentially life-transforming reality. Today, Orchard is advancing a pipeline of HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist. For more information, please visit www.orchard-tx.com. About Kyowa KirinKyowa Kirin aims to discover and deliver novel medicines and treatments with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients with high unmet medical needs, such as bone & mineral, intractable hematological diseases/hemato oncology, and rare diseases. A shared commitment to our values, to sustainable growth, and to making people smile unites us across the globe. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com. ______________________________iMahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature. Journal of Child Neurology 2010, DOI: http://doi.org/10.1177/0883073809341669