Cardiomegaly

SBT-589 showed mitochondrial protection across models of Friedreich's ataxia SBT-589 displayed cardioprotective effects in aggressive mouse model of FA cardiomyopathy Ongoing studies are expected to build on these insights as SBT-589 progresses through developmental stage-gates NEEDHAM, Mass., March 19, 2024 /PRNewswire/ -- Stealth BioTherapeutics Inc. (the "Company" or "Stealth"), a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for diseases involving mitochondrial dysfunction, announced today the presentation of new SBT-589 data demonstrating cardioprotective effects across pre-clinical models of Friedreich's ataxia (FA). The data were presented at the Wellcome Trust Conference on Mitochondrial Medicine – Therapeutic Development, held March 18-20, 2024, in Cambridge, England. FA is a chronic disease of metabolic disruption that is typically diagnosed in childhood or adolescence, is inexorably progressive and usually results in premature death from cardiomyopathy or heart failure. There are no approved therapies for the progressive cardiomyopathy, which is linked to severe mitochondrial dysfunction, and is the leading cause of early death in this devastating disease. SBT-589 is a promising novel molecule that acts on mitochondrial pathways essential for cellular health and energy production that are impaired in FA cardiomyopathy. To evaluate the potential of SBT-589 in FA, a series of studies were conducted in FA patient-derived cells, isolated heart mitochondria, and an aggressive mouse model of FA cardiomyopathy. SBT-589 improved bioenergetics in FA patient-derived cells and mitochondria. In an FA mouse model with prominent cardiac hypertrophy and aggressive mortality, mice treated with once-daily SBT-589 displayed significantly reduced cardiac hypertrophy and a delay in the onset of mortality compared to vehicle-treated mice. "Mitochondrial dysfunction is a central contributor to pathology in Friedreich's ataxia, a disease in which heart failure and sudden cardiac events are among the leading causes of mortality," said David A. Brown, Senior Vice President, Discovery. "Mitigating heart disease in FA is central to Stealth's ongoing efforts to improve the lives of individuals with FA. The new findings presented today support continued development of SBT-589 as a potentially disease-modifying therapy to address the unmet need in cardiomyopathy associated with Friedreich's ataxia." The data were presented by Dr. Laura E. Kropp, Senior Manager of Discovery Biology at Stealth, and recipient of the Keith Michael Andrus Cardiac Award from the Friedreich's Ataxia Research Alliance. About Friedreich's Ataxia Friedreich's ataxia is a rare genetic disease affecting an estimated 1 in 50,000 individuals in the United States. The disease is caused by a defect in the frataxin gene resulting in a relative deficiency of frataxin, leading to mitochondrial iron accumulation and oxidative stress. More than 90% of patients with Friedreich's ataxia experience progressive cardiomyopathy which usually becomes fatal by early adulthood and is the leading cause of early mortality. About Stealth BioTherapeutics Stealth BioTherapeutics is a clinical-stage biotechnology company focused on the discovery, development, and commercialization of novel therapies for age-related and rare genetic diseases involving mitochondrial dysfunction. The Company is initiating Phase 3 clinical trials of elamipretide, its lead investigational product candidate, in dry age-related macular degeneration. Elamipretide is also being tested in a fully enrolled Phase 3 clinical trial in primary mitochondrial myopathy, a rare skeletal myopathic disease caused by nuclear DNA mutations, and is the subject of a New Drug Application for Barth syndrome, an ultra-rare cardioskeletal disease. The Company is evaluating its second-generation clinical-stage candidate, SBT-272, for ophthalmic and neurological disease indications. The Company has a deep pipeline of novel mitochondria-targeted compounds under evaluation as therapeutic product candidates. Several of these lead compounds, including SBT-589, have progressed through pre-clinical development stage-gates and toward IND-enabling studies. Investor Contact Kendall Investor Relations Adam Bero, Ph.D. [email protected] [email protected] Media Contact Anna Stallman Communications Anna Stallman [email protected] SOURCE Stealth BioTherapeutics Inc.

— Company ends 2023 with approximately $123.6 million in cash and investments. Combined with gross proceeds from $108.9 million private placement in January, Solid has anticipated cash runway into 2026 — — FDA cleared IND and granted Fast Track Designation and Orphan Drug Designation for Duchenne muscular dystrophy (Duchenne) gene therapy candidate SGT-003 with patient dosing in Phase 1/2 trial expected Q2 2024 — — Company entered into non-exclusive licensing agreement for use of its proprietary, muscle-targeted AAV-SLB101 capsid — CHARLESTOWN, Mass., March 13, 2024 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a business update. "2023 was an exciting and transformational year for Solid where we completed the integration with AavantiBio, while diversifying and expanding our pipeline. We strengthened our management team with the hiring of a CMO, Dr. Gabriel Brooks, and CFO, Kevin Tan, and advanced our next generation gene therapy for Duchenne, SGT-003, towards the clinic with IND clearance in Q4 and received Fast Track Designation and Orphan Drug Designation in Q4 2023 and Q1 2024, respectively. We continued to bring in additional assets, including SGT-501 for the treatment of a fatal childhood disease called CPVT from ICS Maugeri, while moving additional high potential programs and capsids through preclinical models,” said Bo Cumbo, President and CEO of Solid Biosciences. “We enter 2024 with significant momentum from our recently completed financing in January which raised $108.9 million from a syndicate of leading investors. 2024 will be a year of execution and we look forward to rapidly bringing SGT-003 into the clinic, advancing SGT-501 towards IND filing and most importantly, continuing to bring hope to all those suffering from devastating genetic diseases.” Company Updates Solid expects to initiate dosing in the Phase 1/2 trial of SGT-003 in pediatric patients with Duchenne in the second quarter of 2024. A safety update is expected mid-year and initial data from the first two cohorts of the trial is expected in Q4 2024. Solid announced it expects to IND for its first cardiac gene therapy candidate, SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), in the first quarter of 2025. Solid has entered into a non-exclusive licensing agreement for use of its proprietary, muscle-targeted AAV-SLB101 capsid. Solid aims to license AAV-SLB101 broadly to both companies and academic institutions pursuing treatments for rare diseases. Recent Company Highlights On January 16, 2024, Solid announced that the FDA granted Orphan Drug Designation for its Duchenne gene therapy candidate SGT-003. This designation provides certain benefits, including specified financial incentives, to support clinical development and the potential for up to seven years of market exclusivity in the U.S. upon regulatory approval. On January 8, 2024, Solid announced a $108.9 million private placement with new and existing investors. The Company expects to use net proceeds of $104.0 million from the private placement to fund ongoing pipeline development programs, business development activities, and for working capital and other general corporate purposes. On December 7, 2023, Solid announced the FDA granted Fast Track Designation for SGT-003. The Fast Track program facilitates the expedited development and review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. On November 14, 2023, Solid announced that it had received FDA clearance for the Phase 1/2 trial of SGT-003. Fourth Quarter and Full-Year 2023 Financial Highlights There were no collaboration revenues for the fourth quarter of 2023 and 2022. There were no collaboration revenues for the full year ended December 31, 2023, compared to $8.1 million for the full year ended December 31, 2022. Collaboration revenue in 2022 was related to research services and cost reimbursement from the Collaboration Agreement with Ultragenyx, which the Company entered in the fourth quarter of 2020. Research and development expenses for the fourth quarter of 2023 were $15.4 million, compared to $21.3 million for the fourth quarter of 2022. Research and development expenses for the full year ended December 31, 2023, were $76.6 million, compared to $78.4 million for the full year ended December 31, 2022. The decrease of $1.8 million in research and development expenses was primarily due to a decrease in expenses related to SGT-001 due to our decision to prioritize SGT-003, offset by an increase in costs for SGT-003 and SGT-501. General and administrative expenses for the fourth quarter of 2023 were $6.8 million, compared to $7.6 million for the fourth quarter of 2022. General and administrative expenses for the full year ended December 31, 2023, were $27.8 million, compared to $28.9 million for the full year ended December 31, 2022. Net loss for the fourth quarter of 2023 was $20.3 million, compared to $15.2 million for the fourth quarter of 2022. Net loss for the full year ended December 31, 2023, was $96.0 million, compared to $86.0 million for the full year ended December 31, 2022. The increase in net loss was primarily related to a gain on acquisition and collaboration revenue in 2022, offset by decreased research and development costs, decreased general and administrative expenses, and an increase in yields on cash equivalents and available-for-sale securities in 2023. Solid had $123.6 million in cash, cash equivalents, and available-for-sale securities as of December 31, 2023, compared to $213.7 million as of December 31, 2022. The Company expects that its cash, cash equivalents, and available-for-sale securities as of December 31, 2023, together with the net proceeds from the January 2024 private placement, will enable it to fund key strategic priorities into 2026. About Solid Biosciences Solid Biosciences is a life sciences company focused on advancing a portfolio of gene therapy candidates including SGT-003 for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit . Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding future expectations, plans and prospects for the company; the ability to successfully achieve and execute on the company’s priorities and achieve key clinical milestones; the company’s SGT-003 program, including expectations for initiating dosing and availability of clinical trial data; the company’s expectations for submission of an IND for SGT-501; Solid’s plans to license AAV-SLB101 broadly to both companies and academic institutions; the anticipated use of proceeds from the January 2024 private placement; the cash runway of the company and the sufficiency of the Company’s cash, cash equivalents, and available for sale securities to fund its operations; and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” “working” and similar expressions. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include, but are not limited to, risks associated with the ability to recognize the anticipated benefits of Solid’s acquisition of AavantiBio; the company’s ability to advance SGT-003, SGT-501, AVB-401 and other preclinical programs and capsid libraries on the timelines expected or at all; obtain and maintain necessary approvals from the FDA and other regulatory authorities; replicate in clinical trials positive results found in preclinical studies of the company’s product candidates; obtain, maintain or protect intellectual property rights related to its product candidates; compete successfully with other companies that are seeking to develop Duchenne and other neuromuscular and cardiac treatments and gene therapies; manage expenses; and raise the substantial additional capital needed, on the timeline necessary, to continue development of SGT-003, SGT-501, AVB-401 and other candidates, achieve its other business objectives and continue as a going concern. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the company’s actual results to differ from those contained in the forward-looking statements, see the “Risk Factors” section, as well as discussions of potential risks, uncertainties and other important factors, in the company’s most recent filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company's views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so. Solid Biosciences Contact: Leah Monteiro VP, Investor Relations and Communications 617-766-3430 lmonteiro@solidbio.com

LA JOLLA, Calif., March 12, 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 that MediciNova’s collaborator, Perenlei Enkhbaatar, MD, PhD, FAHA, Professor, Department of Anesthesiology, Director, Translational Intensive Care Unit, Charles Robert Allen Professor in Anesthesiology, University of Texas Medical Branch, presented new data and results of a nonclinical study evaluating MN-166 (ibudilast) in a chlorine gas-induced acute lung injury (CIALI) model at the Society of Toxicology (SOT) 63rd Annual Meeting and ToxExpo in Salt Lake City, Utah. The primary objective of this nonclinical efficacy study was to determine the safety and pharmacological activity of MN-166 (ibudilast) following ALI induced by chlorine (Cl2) gas inhalation in a clinically relevant translational ovine model. In this study, single-dose and multi-dose treatments were evaluated. The primary endpoint was the mean change in the pulmonary function measure PaO2/FiO2, which is the ratio of arterial oxygen partial pressure to fractional inspired oxygen. Additional endpoints included survival, lung mechanics, lung injury, and edema formation evaluated by chest x-ray. The highlights of the presentation, entitled “Evaluation of safety and pharmacological activity of MN-166 (ibudilast) in a clinically relevant ovine model of chlorine-induced acute lung injury” (Abstract # 4296), are as follows: After a Cl2 gas challenge (210 ppm x 30 min) to induce moderate ALI (mean PaO2/FiO2<200 mmHg), the test subjects were randomly assigned to 4 treatment groups: MN-166 (ibudilast) low dose (10 mg) or high dose (20 mg), a positive control (rolipram 1 mg), and vehicle (negative control). Cl2 gas concentration of 210 ppm x 30 min was expected to result in a 20 - 30% mortality rate (Fukuda 2015). Treatment regimens: Single-dose treatment (n=5/group) in which a 30-min IV infusion was given once only, initiated 30 min after completion of the Cl2 challenge Multi-dose treatment (n=3/group) in which 30-min IV infusions were given a total of 4 times, initiated 30 min after the completion of Cl2 gas challenge, then every 12 hours Efficacy Result Single-dose treatment MN-166 (ibudilast) 20 mg and rolipram treatment resulted in greater improvement in mean PaO2/FiO2 and peak airway pressure but dissipated after Hour 12 Multi-dose treatment MN-166 (ibudilast) 20 mg showed greater improvement in mean PaO2/FiO2 ratio (p=0.0001), with animals recovering enough to no longer meet the criteria of ARDS (Berlin ARDS definition 2012) MN-166 (ibudilast) 20 mg also showed greater improvement in peak airway pressure (p<0.05), plateau airway pressure (p<0.05), pulmonary artery pressure (p<0.05), and lung injury score (p<0.05) compared to the other treatment groups MN-166 (ibudilast) 20 mg also maintained cardiac and kidney function compared to the other treatment groups Notably, significance was observed beyond the T=12-hour timepoint, further reinforcing the observed benefit of MN-166 (ibudilast) 20 mg with the multi-dose treatment regimen Survival MN-166 (ibudilast) 20 mg treatment demonstrated a greater survival benefit than the other treatment groups. All animals in the MN-166 (ibudilast) 20 mg group (8 out of 8) survived the 48-hour monitoring period, while 25% (2 out of 8 / arm) animals were euthanized early in other groups upon reaching the euthanasia criteria. Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc., commented, "We are very pleased to report the positive results in which MN-166 demonstrated a large and significant improvement in pulmonary function and recovery, i.e., no longer having ARDS, attenuation of lung injury, and a higher survival rate in the ovine CIALI model study. Collectively, positive findings from this clinically relevant ovine model, the previously reported lipopolysaccharide (LPS)-induced ARDS nonclinical model, and significant positive results from a clinical trial in hospitalized COVID-19 patients at risk of developing ARDS, we believe MN-166 (ibudilast) shows promise as a candidate for ALI.” This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority, under contract number 75A50121C00022. 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 pro 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: Geoff O'Brien Vice President MediciNova, Inc. info@medicinova.com