Hesperos, Inc.

ORLANDO, Fla.--( BUSINESS WIRE )--Hesperos, a leader in recreating human biology for drug discovery, is pleased to announce its Human-on-a-Chip ® technology played a role in supporting a client’s Investigational New Drug submission with the Food & Drug Administration for a Phase II clinical trial of its investigational product DNTH103, highlighting the contribution of in vitro proof-of-concept data. Dianthus Therapeutics, Inc. is currently conducting a Phase II trial of DNTH103, a potent monoclonal antibody that selectively targets the classical pathway of the complement system, for the treatment of generalized myasthenia gravis (gMG) [ NCT06282159 ]. gMG is a chronic autoimmune disorder triggered by the production of antibodies that interfere with muscle nerve signal transmission and lead to muscle weakness. Hesperos’ proprietary neuromuscular junction (NMJ) model interconnects human cell compartments with devices that monitor muscle contraction and electrical activity in real-time, providing physiologically relevant functional readouts. Hesperos researchers demonstrated that, in the presence of gMG patient serum, DNTH103 can improve nerve cell transmission and thus decrease muscle fatigue in their preclinical NMJ model. Dianthus presented these data at the American Academy of Neurology (AAN) Annual Meeting, which took place April 13-18, 2024 in Denver, Colorado and virtually and at the 10 th Congress of the European Academy of Neurology (EAN), which took place June 29-July 2, 2024 in Helsinki. These presentations can be found in the Scientific Publications section of the Dianthus website. “We are pleased that our Human-on-a-Chip ® model further validates the potential role of DNTH103 as a treatment for gMG and supported Dianthus’ FDA submission for its Phase II gMG clinical trial,” said Lawrence Florin, CEO, Hesperos, Inc. Hesperos, Inc. Hesperos is a global contract research organization (CRO) specializing in preclinical drug development services through its Human-on-a-Chip ® platform. By replicating key aspects of human biology (and thus avoiding expensive, time-consuming and often less informative animal testing), Human-on-a-Chip ® platform models provide product development teams with more meaningful insights that can accurately predict an agent’s therapeutic profile while lowering costs and accelerating development timelines. www.hesperosinc.com

ORLANDO, Fla.--( BUSINESS WIRE )--Researchers from Hesperos and the University of Central Florida have developed a groundbreaking model using human induced pluripotent stem cell (iPSC)-derived cortical neurons to better understand and combat Alzheimer’s disease (AD). Their study, “ A functional aged human iPSC-cortical neuron model recapitulates Alzheimer’s disease, senescence, and the response to therapeutics ," has been published in the prestigious journal Alzheimer's & Dementia ® : The Journal of the Alzheimer's Association. doi.org/10.1002/alz.14044 AD affects an estimated 6.2 million Americans aged 65 and older, with projections suggesting this number could reach 14 million by 2050. Current treatments, such as acetylcholinesterase inhibitors and NMDA receptor antagonists, provide only temporary relief. The high failure rate of AD clinical trials highlights the need for a better understanding of the pathophysiology and drug mechanisms. The study addresses a critical challenge in Alzheimer’s research: the degeneration of cortical layers associated with cognitive decline. Despite substantial efforts to date, few current AD therapies are not disease-modifying. The team accurately reproduced key biological aspects of aging and senescence in a multi-cellular microphysiological system (MPS), also known as a Human-on-a-Chip. This new approach reveals how cellular aging, also known as senescence, contributes to disease progression and therapy resistance, providing researchers with an accurate, human platform to further understand the disease and potential therapeutics in a living context. Further, since other platforms at Hesperos, based on neurodegenerative diseases, have been accepted by the Food and Drug Administration (FDA) for efficacy data, it provides a new method to accelerate development and regulatory submissions of new treatments. This model provides an invaluable tool for real-time measurement of neuronal activity and aging biomarkers, facilitating drug screening and the development of AD therapies. It also reveals complex disease mechanisms, such as the role of inflammatory factors in neuronal senescence and how it differs from non-disease age-related controls, offering new targets for intervention. Researchers cultured human iPSC-derived cortical neurons on patterned microelectrode arrays to measure long-term potentiation (LTP) noninvasively. LTP, a quantifiable metric for learning and memory, is directly impacted by central nervous system neurodegeneration. By treating these neurons with pathogenic amyloid-β (Aβ), a peptide that plays a central role in development of AD, to mimic disease pathophysiology, the team was able to analyze senescence and therapeutic responses. The study demonstrates that this novel human iPSC-cortical neuron model of aging, cultured in serum-free, defined conditions, accurately recapitulates hallmarks of AD showing the following: Pathological Insights : Aβ42 induced synaptic damage, accelerated neuronal senescence, impaired mitochondrial potential, and increased reactive oxygen species (ROS), leading to oxidative stress and inflammation. Therapeutic Responses : Drugs such as memantine, rolipram, saracatinib, and donepezil improved neuronal function and viability, though they did not completely halt Aβ42-driven senescence. The study underscores the potential of biomimetic MPS systems in translational research. By integrating clinically relevant neuronal function with proteome responses, this platform is poised to accelerate the discovery of novel neuroprotective compounds for AD and other neurological disorders. “This marks a significant step forward in Alzheimer's research by providing a deeper understanding of AD pathophysiology in a human aged MPS platform. We are excited about the potential of this model to transform drug discovery in AD, providing hope for patients,” said J. Hickman, PhD, co-founder and Chief Scientist of Hesperos and Professor of Chemistry at UCF. This research was supported by grants from the National Institutes of Health (R44TR001326, R44AG058330). Research Article : doi.org/10.1002/alz.14044 Nanoscience Technology Center (NSTC) at the University of Central Florida (UCF) The mission of the NSTC is to establish a cutting-edge research program in materials and nanotechnology, provide high quality training for students and facilitate the advance of innovations to solve real world technology challenges. https://nanoscience.ucf.edu/ Hesperos, Inc. Hesperos is a global contract research organization (CRO) providing drug development services using its Human-on-a-Chip ® platform - the most advanced, multi-organ microphysiological systems available today. https://hesperosinc.com

ORLANDO, Fla.--(BUSINESS WIRE)-- A research team from the University of Central Florida and Hesperos, a pioneer in human-on-a-chip technology, has developed the first human model to study the effects of an opioid overdose and reversal with naloxone. The study, "Human IPSC-Derived PreBötC-like Neurons and Development of an Opiate Overdose and Recovery Model" (doi.org/10.1002/adbi.202300276) was published in Advanced Biology on September 7, 2023. The paper describes the development of human preBötC neurons from induced pluripotent cells (iPSCs) and the establishment of a human model that mimics opioid overdose with four opioids and the recovery of neuronal activity with naloxone treatment. “I am incredibly proud of our team's groundbreaking work that will provide invaluable insights into understanding opioid addiction and recovery, paving the way for more effective treatments and ultimately saving lives. We hope this exciting first step will play a significant role in understanding and developing treatment solutions for this devastating crisis.” - J Hickman, Professor UCF and Chief Scientist, Hesperos The PreBötC brain region is responsible for automatic breathing regulation and is what shuts down first during an overdose (causing asphyxiation and ultimately death). The dose-dependent inhibition of these neurons’ activity was demonstrated with four opioids, including Fentanyl - the primary culprit of overdose deaths. Naloxone, the most widely used recovery medication, was used in each case to rescue activity, further replicating the response seen in patients. Opioid overdose is the leading cause of drug lethality, posing an urgent need for investigation. Prior to this study, the best models available have been animal based which are known to have limited translation to humans. The development of this human model is a significant advancement in the field, bringing the medical community closer to finding a solution to this public health emergency. “This research provides an accurate way to model overdose in the lab, using human brain cells programmed to respond to many different opioids,” said Rebecca Baker. Ph.D., Director of the Helping to End Addiction Long-term® Initiative, or the NIH HEAL Initiative®, at the National Institutes of Health (NIH). “Amid an increasingly deadly opioid crisis, this tool can be used to screen medications to reverse overdoses from potent synthetic opioids like fentanyl.” This is the first step of the project that seeks to establish a five-organ, Human-on-a-Chip, including PreBötC neurons, liver, heart, kidney, and skeletal muscle, to monitor organ-specific, functional changes through each opiate-induced overdose and rescue to understand not only the effect of overdose but repeat application of naloxone for off-target toxicity of the non-neuronal organ constructs. The project was funded by the National Center for Advancing Translational Sciences (NCATS) as part of NIH’s HEAL Initiative. Established in 2018, the HEAL Initiative is an aggressive effort to find scientific solutions that improve the understanding and treatment of opioid addiction. “This system has implications for drug discovery and the development of more effective personalized medicines to combat the opioid crisis,” said Danilo Tagle, Ph.D., from NCATS. “It has potential as an alternative to animal models in determining effects of biological therapeutics, including pair modulations and alternatives to naloxone.” UCF, Hybrid Systems Lab The Hybrid Systems Laboratory (HSL) within the NanoScience Technology Center (NSTC) at the University of Central Florida (UCF) has established a collaborative environment between four faculty members with expertise in surface interface chemistry and BioMEMS platforms, a stem cell biologist and electrophysiologist, a neuroscientist, and a systems biology engineer. This has created a trans-disciplinary environment where post-docs, students and staff with backgrounds as diverse as theoretical physics, chemistry, engineering, molecular biology, cell biology and electrophysiology work side-by-side in a world class facility. These facilities, plus the remainder of the facilities within the NSTC, and also located within the rest of UCF create a first class environment for research. About Hesperos Hesperos, Inc. is a leader in efforts to characterize an individual’s biology to better understand disease states and the human response to therapeutics. As a global contract research organization (CRO), Hesperos offers preclinical safety and efficacy testing services using its Human-on-a-Chip® platform – the most advanced, multi-organ microphysiological systems available today. Our mission is to accelerate drug discovery by enabling unprecedented insight into how the human body will respond to chemicals and novel therapeutics. More information is available at . Funding Support: NIH Grant 4UH3TR003081-02 Publication: doi.org/10.1002/adbi.202300276