Portfolio: Development status
Our lead asset, vector construct EG110A, has been designed to express a botulinum toxin fragment in bladder sensory neurons, whilst preserving motor neuron and muscle cell function. EG110A has shown Proof-of-Concept efficacy in relevant animal models for overactive bladded from neurologic origin (NDO) or not (OAB), and an IND data package is being prepared for submission. The clinical development plan unfolds into multiple indications to eventually a broad product labelling.
Neurogenic Detrusor Overactivity (NDO)
The company’s primary focus is to treat a common urinary bladder dysfunction caused by spinal cord injury (SCI) and other neurodegenerative diseases such as multiple sclerosis (MS). This is the neurological disease known as neurogenic detrusor overactivity (NDO), responsible for various degrees of incontinence, as well as urinary tract infections and renal (kidney) damage than can lead to death in 5-10% of SCI population. NDO affects almost all (85-90%) of patients with SCI1 , half of those with MS2 , and a third of those with Parkinson’s disease, and impacts on an individual’s independence and dignity. Over time, most patients do not respond to the standard pharmacological approaches to treatment, such as oral antimuscarinics or botulinum toxin injections. All those treatments aim at inhibiting the bladder muscle itself and there is therefore the associated need to empty the bladder using catheterization which is a high-risk factor for urinary infections.
1 Hamid, R., Averbeck, M.A., Chiang, H. et al. Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury. World J Urol 36, 1517–1527 (2018). https://doi.org/10.1007/s00345-018-2301-z
2 Phé V et al., nrurol.2016.53 doi:10.1038, Management of neurogenic bladder in patients with MS
Overactive Bladder (OAB)
Ranging from light to highly debilitating forms, overactive bladder is a very common disease affecting 15-33% of general population3, with a strong unbalance towards women, characterized by the urgent need to go to the bathroom up to 40 times per day, with or without incontinence. Major impact on quality of life and self-esteem is concurrent with mental health impact with depression and anxiety.
3 Reynolds, W. S., Fowke, J., & Dmochowski, R. (2016). The Burden of Overactive Bladder on US Public Health. Current bladder dysfunction reports, 11(1), 8–13. https://doi.org/10.1007/s11884-016-0344-9
Interstitial Cystitis – Painful Bladder Syndrome (IC/PBS)
Defined as a chronic pain from the pelvic area in the absence of urinary infection, IC/PBS is estimated to affect 0.9% of US population4, with a 2-fold increase incidence over the past decades5. Those patients have however very limited medical options with only one approved drug that have demonstrated limited effects.
4 Anger, J. T., Dallas, K. B., Bresee, C., De Hoedt, A. M., Barbour, K. E., Hoggatt, K. J., Goodman, M. T., Kim, J., & Freedland, S. J. (2022). National prevalence of IC/BPS in women and men utilizing veterans health administration data. Frontiers in pain research (Lausanne, Switzerland), 3, 925834. https://doi.org/10.3389/fpain.2022.925834
5 Payne CK, Joyce GF, Wise M, Clemens JQ. Urologic Diseases in America Project. Interstitial cystitis and painful bladder syndrome. J Urol. (2007) 177:2042– 9. doi: 10.1016/j.juro.2007.01.124
Over time, most NDO and OAB patients do not respond to the standard pharmacological approaches to treatment, such as oral antimuscarinics and beta-3 agonists that have systemic off-target effects and are thus poorly tolerated by many patients. Local injections of botulinum toxins basically paralyse the bladder muscle, thus requiring in 15% of cases, patients to empty their bladder using catheterization 4 to 6 times a day, with an associated higher risk of urinary infections. For OAB, implantable medical devices have been approved requiring costly surgical procedures.
EG110A for NDO, OAB and IC/PBS could bring the expected long-term and truly local efficacy, to multiple hundred thousand of patients across these indications. It thus represents a major market opportunity of multi-billion-dollar revenues, in an innovation poor environment.
Using the characteristics of our nrHSV-1, our vector selectively silences the sensory nerves of the bladder responsible for conveying pathogenic signal in these different indications. Preserving the ability of the bladder to contract, we want to offer patient suffering from NDO and OAB a long-lasting treatment that restores continence and preserves volitional voiding either naturally or stimulated. Targeting the sensory nerves, we also aim to reduce the urgency symptom in OAB, and selectively kill the pain sensation in IC/PBS, thus addressing in both cases the most important issue.
What Key Opinion Leaders think
"Neurogenic bladder overactivity in spinal cord injury patients is a severe condition leading to urinary incontinence and may have a significant impact on their kidneys – a new treatment is needed which offers new alternatives.
EG427 with its novel approach using targeted gene therapy potentially provides a unique and long-lasting new therapy which is being developed to treat this group of patients and is currently under evaluation."
Prof. Christopher Chapple, BSc, MBBS, MD, FRCS (Urol), FEBU, FCSHK (Hon)
Emeritus Consultant Urological Surgeon, Sheffield Teaching Hospitals NHS Foundation Trust
Honorary Professor, University of Sheffield
Visiting Professor, Sheffield Hallam University
“There is a pressing need for efficacious treatment options for people suffering from neurologic bladder conditions. A targeted and long -lasting therapy, such as what EG110A could offer would meet these needs. Its focus on bladder sensory neurons offers the potential for long lasting effect without impacting the voiding function.”
Prof. Roger Dmochowski
Professor of Urology and Surgery at Vanderbilt University Medical Center