SBT-272 / Stealth BioTherapeutics - LARVOL DELTA

Stealth BioTherapeutics Awarded Grant from The Michael J. Fox Foundation to Support Development of SBT-272 in Parkinson's Disease (PRNewswire) - "Stealth BioTherapeutics...announced that The Michael J. Fox Foundation for Parkinson's Research (MJFF) awarded a research grant to evaluate Stealth's mitochondria-targeted molecule, SBT-272, for Parkinson's disease (PD). The preclinical study is expected to inform the development of SBT-272 for PD by accelerating identification of biomarkers of mitochondrial dysfunction."

Financing • CNS Disorders • Parkinson's Disease

SBT-272 improves TDP-43 pathology in ALS upper motor neurons by modulating mitochondrial integrity, motility, and function. (PubMed, Neurobiol Dis) - "In comparison to edaravone and AMX0035, SBT-272 appeared more effective in restoring health of diseased UMNs. Chronic treatment of SBT-272 for sixty days starting at an early symptomatic stage of the disease in vivo led to a significant reduction in astrogliosis, microgliosis, and TDP-43 pathology in the ALS motor cortex. Our results underscore the therapeutic potential of SBT-272, especially within the context of TDP-43 pathology and mitochondrial dysfunction."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • Metabolic Disorders • Proteinopathy • TARDBP

Stealth BioTherapeutics Announces SBT-272 Data Updates and Orphan Drug Designation for the Treatment of Amyotrophic Lateral Sclerosis (ALS) (PRNewswire) - P1 | N=NA | "Stealth BioTherapeutics Corp...announced encouraging Phase 1 data on the safety and tolerability of SBT-272....The Company also announced that positive preclinical data demonstrating that treatment with SBT-272 provided neuroprotection of upper motor neurons harboring ALS pathology will be presented today at the Northeast Amyotrophic Lateral Sclerosis (NEALS) conference in Clearwater, FL. The Company recently received Orphan Drug Designation from the US Food and Drug Administration (FDA) Office of Orphan Products Development for SBT-272 for the treatment of patients with ALS....Interim results from the Phase 1 study for SBT-272 demonstrated that selected doses are anticipated to result in therapeutic concentrations in the brain based on observed drug levels achieved in preclinical studies. While final safety analyses are ongoing, dose levels identified for subsequent clinical evaluation appear generally safe and well tolerated..."

Orphan drug • P1 data • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

[PREPRINT] SBT-272 improves TDP-43 pathology in the ALS motor cortex by modulating mitochondrial integrity, motility, and function (bioRxiv) - “We investigated whether SBT-272 can improve IMM structure and health in UMNs diseased with TDP-43 pathology in our well-characterized UMN reporter line for ALS. We found that SBT-272 significantly improved mitochondrial structural integrity and restored mitochondrial motility and function. This led to improved health of diseased UMNs in vitro. In comparison to edaravone and AMX0035, SBT-272 appeared more effective in restoring health of diseased UMNs. Chronic treatment of SBT-272 for sixty days starting at an early symptomatic stage of the disease in vivo led to a reduction in astrogliosis, microgliosis, and retention of UMN degeneration in the ALS motor cortex. Our results underscore the therapeutic potential of SBT-272, especially within the context of TDP-43 pathology and mitochondrial dysfunction."

Preclinical • Preprint • Amyotrophic Lateral Sclerosis • CNS Disorders

Platform for Screening Compounds for Treatment of AMD Using iPSC-derived Human RPE: Examples Using Elamipretide and SBT-272 (ASRS 2022) - No abstract available

Stealth BioTherapeutics Presents New SBT-272 Data Demonstrating Improvement in Upper Motor Neuron Function in ALS Disease Model at Keystone Neurodegeneration Symposium (PRNewswire) - "Stealth BioTherapeutics Corp...announced today the presentation of new SBT-272 preclinical data demonstrating functional improvement in upper motor neurons with TDP-43 pathology, which plays a significant role in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The data were presented at the Keystone Neurodegeneration Symposium in Keystone, CO held June 5-9, 2022....SBT-272 significantly improved mitochondrial structural integrity and motility in TDP-43 mutant (A315T)-expressing upper motor neurons. These enhancements in mitochondrial health were associated with improved axon outgrowth, a key indicator of improved neuronal health. The effect of SBT-272 on axon outgrowth was superior to edaravone (approved for the treatment of ALS) and AMX0035 (NDA under FDA review). Chronic in vivo administration of SBT-272 reduced upper motor neuron degeneration and neuroinflammation in the motor cortex of the prp-hTDP-43A315T-UeGFP mouse model of ALS..."

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

Stealth BioTherapeutics Announces New SBT-272 Data and Trial Initiation (PRNewswire) - “Stealth BioTherapeutics Corp…announced today the presentation of new SBT-272 preclinical data at the Mitochondrial Biochemistry in Health and Disease Symposium in Breckenridge, CO and dosing of the first subject in its Phase 1 clinical trial of SBT-272….The new data demonstrated behavioral and metabolic improvements with SBT-272 in a mouse model of Huntington's disease. In the study, mice were treated for up to 8 weeks with daily SBT-272 and displayed significantly improved motor function compared to vehicle-treated mice….The Phase 1 clinical trial…enrolling up to 64 healthy subjects across multiple cohorts….As a primary objective, the study will evaluate safety and tolerability of single and multiple ascending doses of SBT-272.”

New P1 trial • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Huntington's Disease • Multiple System Atrophy • Parkinson's Disease

"SBT-272 Offers Mitochondrial Protection in ALS https://t.co/1RcGsVVEip #ALS #amyotrophiclateralsclerosis #SBT272 #medicalresearch #NEALSmeeting @alsassociation" (@PatientWorthy)

Amyotrophic Lateral Sclerosis • CNS Disorders

Stealth BioTherapeutics Presents Positive SBT-272 Preclinical Data at 2021 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting (Yahoo Finance) - “Stealth BioTherapeutics Corp…announced today the presentation of new promising data from a study evaluating the effects of SBT-272 in a murine model of amyotrophic lateral sclerosis (ALS). The data were presented at the virtual 2021 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting held October 6-7, 2021…‘we plan to advance SBT-272 in dose-ranging Phase 1 clinical studies early next year.’”

New P1 trial • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

[VIRTUAL] The mitochondrial targeted drug SBT-272 attenuates dopaminergic neuron loss, alpha-synuclein burden and neuroinflammation in a mouse model of Parkinson's Disease (MDS Congress 2021) - "SBT-272 prevented the loss of dopaminergic neurons, decreased phosphorylated alpha-synuclein burden and attenuated neuroinflammation in the substantia nigra following mutant alpha-synuclein induced toxicity in mice. These data support further investigation of SBT-272 for treating neurodegenerative disease caused by alpha-synucleinopathy, such as PD and Multiple Systems Atrophy."

Preclinical • CNS Disorders • Multiple System Atrophy • Parkinson's Disease • GFAP

Stealth BioTherapeutics Presents Positive SBT-272 Preclinical Data at International Parkinson and Movement Disorder Society Virtual Congress 2021 (PRNewswire) - "Stealth BioTherapeutics Corp...announced today the presentation of new promising data from a study evaluating the effects of SBT-272 in a murine model of Parkinson's disease (PD)....The data were presented at the International Parkinson and Movement Disorder Society Virtual Congress 2021. In the study, mice were injected with viral particles that over-express human A53T alpha-synuclein...in the substantia nigra....Following the injection, the mice displayed PD pathology, including a significant loss of dopaminergic neurons....In addition, the animals displayed aggregation of alpha-synuclein and markers of neuroinflammation. Systemic daily administration of SBT-272 at two different doses significantly protected against the loss of dopaminergic neurons and the aggregation of pathological alpha-synuclein. In addition, the higher dose of SBT-272 significantly reduced two different markers of neuroinflammation."

Preclinical • CNS Disorders • Parkinson's Disease

Stealth BioTherapeutics Reports Fiscal Year 2020 Financial Results And Recent Business Highlights (PRNewswire) - "SBT-272: The Company is conducting toxicology studies to support a potential Phase 2a clinical study in patients with neurological disease in 2022....Expansion of neurology franchise: The Company is continuing its neurology pipeline expansion efforts with SBT-272...expects to announce results of SBT-272 preclinical studies...during 2021."

New P2a trial • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Multiple System Atrophy

Stealth BioTherapeutics Reports Third Quarter 2020 Financial Results And Recent Business Highlights (BioSpace) - "SBT-272...With these encouraging results, the Company is assessing drug exposure to inform decisions regarding oral formulation and utility of exploring subcutaneous dosing. Long term toxicology studies are expected to be conducted in 2021 to enable progression into Phase 2 trials....Data presented at the 2020 Annual NEALS Meeting in October demonstrated that SBT-272 improved neurite length and branching in mutant TDP43 primary upper motor neurons. TDP43 pathology has been observed in multiple neurodegenerative diseases, including ALS, Frontotemporal Lobar Degeneration (FTLD), Lewy Body Dementia (LBD), Progressive Supranuclear Palsy (PSP), and Alzheimer's Disease, and is believed to play a role in neuronal cell death."

Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Lewy Body Disease • Multiple System Atrophy • Parkinson's Disease • Progressive Supranuclear Palsy

Stealth BioTherapeutics Announces Poster Presentation at 2020 Annual NEALS Meeting (PRNewswire) - “Stealth BioTherapeutics…announced that the company will present an abstract in a poster session at the upcoming 2020 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting, which is being held online from September 30th to October 1st….The poster, entitled ‘The mitochondrial targeted peptidomimetic SBT-272 protects cortical spinal motor neurons from mutant TDP43 pathology,’ demonstrates that SBT-272 protects upper motor neurons from mutant TDP43 driven neurodegeneration.”

Biomarker • Amyotrophic Lateral Sclerosis • CNS Disorders • Frontotemporal Lobar Degeneration • Lewy Body Disease • Progressive Supranuclear Palsy

Stealth BioTherapeutics Reports Second Quarter 2020 Financial Results and Recent Business Highlights (StockHouse) - “Stealth BioTherapeutics…today reported financial results for the second quarter ended June 30, 2020 and provided a corporate update….Announcement of pre-clinical data for SBT-272 for the treatment of amyotrophic lateral sclerosis and multiple systems atrophy and for SBT-259 in Charcot-Marie-Tooth disease expected by year-end 2020.”

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

Stealth BioTherapeutics reports first quarter 2020 financial results and recent business highlights (PRNewswire) - “The Company anticipates that preclinical data expected later this year in models of amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) will help inform SBT-272's clinical development pathway for rare neurodegenerative diseases….Pre-clinical data for SBT-272 in ALS and MSA and for SBT-259 in Charcot-Marie-Tooth disease expected by year-end 2020.”

Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Multiple System Atrophy • Proteinopathy

Stealth BioTherapeutics reports fiscal year 2019 financial results and recent business highlights (BioSpace) - "The Company anticipates that preclinical data expected later this year in models of amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) will help inform SBT-272's clinical development pathway for rare neurodegenerative diseases."

Preclinical

Stealth BioTherapeutics initiates first-in-human study of SBT-272 (P&T) - “Stealth BioTherapeutics…announced the initiation of a first-in-human Phase 1 trial evaluating its second generation pipeline compound, SBT-272, in healthy subjects….‘We designed this product candidate for neurodegenerative diseases, aiming to improve potency and blood-brain barrier penetration, and we're encouraged by early signals of its efficacy in a preclinical study in amyotrophic lateral sclerosis (ALS)….’"

New P1 trial

Stealth BioTherapeutics reports third quarter 2019 financial results and recent business highlights (PRNewswire) - “Presented new preclinical data for SBT-272…from a mouse model of amyotrophic lateral sclerosis (ALS) demonstrated a statistically significant, dose-dependent delay in the onset of neurological symptoms as well as a reduction in neurofilament light chain, a systemic marker of neurodegeneration, and prolonged lifespan. SBT-272 is currently in pre-clinical development for treatment of ALS and other rare neurodegenerative diseases involving mitochondrial dysfunction and is expected to advance into Phase 1 by year-end.”

New P1 trial • Preclinical