Versameb demonstrates potential of engineered IGF-I mRNA as a regenerative therapeutic

The paper, entitled ‘Local application of engineered insulin-like growth factor I mRNA demonstrates regenerative therapeutic potential in vivo’, highlights recent findings, which further demonstrate the therapeutic potential of engineered IGF-I mRNA as a regenerative medicine with a favorable safety profile.

The study demonstrated that the local administration of engineered IGF-I mRNA, which ensures desirable homeostatic kinetics and non-systemic, local dose-dependent expression of IGF-I protein, can overcome the unfavorable pharmacokinetic profile of IGF-I which has previously prevented it from being used therapeutically. IGF-I deficiency is associated with several neurological and musculoskeletal diseases due to impaired growth and regeneration. The novel and proprietary technology used to engineer the heterologous signal peptide improved in vitro protein secretion and accelerated in vivo functional regeneration (16-fold) over endogenous IGF-I mRNA, while pre-clinical models confirmed that locally administered IGF-I mRNA remained at the site of injection, contributing to a favorable safety profile. These findings combine to demonstrate the therapeutic potential of engineered IGF-I mRNA and its clinical translatability in different diseases.

Dr Justin Antony Selvaraj, Technology Director of Versameb and first author of the publication, said: “Our study established the therapeutic benefit of engineered IGF-I mRNA in both “acute” muscle injury model and “chronic” spinal disc herniation model. These studies further confirm that locally administered mRNA did not distribute systemically and no local toxicity was observed, rendering a favorable safety profile”.

Dr Klaas Zuideveld, Chief Executive Officer of Versameb, said: “These positive results further validate the potential of mRNA as a safe, regenerative therapeutic for the treatment of Stress Urinary Incontinence (SUI), a high unmet medical need affecting more than 30% of adult women globally with no current drug treatment approved. Our lead candidate, VMB-100, has demonstrated promising pre-clinical data showing muscle tissue regeneration and function restoration of the urinary sphincter and is commencing clinical development in H1 2024, following IND clearance received by the FDA in November 2023. We look forward to providing further details of our first-in-class mRNA therapy in the future as we transform the treatment paradigm for SUI.”

Citation:
Justin S. Antony, Pascale Birrer, Claudia Bohnert, Sina Zimmerli, Petra Hillmann, Hervé Schaffhauser, Christine Hoeflich, Andreas Hoeflich, Ramzi Khairallah, Andreas T. Satoh, Isabelle Kappeler, Isabel Ferreira, Klaas P. Zuideveld, and Friedrich Metzger. Local application of engineered insulin-like growth factor I mRNA demonstrates regenerative therapeutic potential in vivo. Molecular Therapy – Nucleic Acids, Volume 34, 2023, 102055

About VMB-100
VMB-100 is an intramuscularly locally delivered, sequence engineered messenger ribonucleic acid (mRNA) encoding for human insulin-like growth factor-1 (IGF-1) under investigation for the treatment of stress urinary incontinence (SUI). VMB-100 has the potential to become first-and best-in-class in sustained muscle regeneration following short-term treatment. In preclinical studies, it has been demonstrated that VMB-100 induced the expression of IGF-1 levels in human muscle cells. In animal models of SUI, VMB-100 accelerated regeneration of the urinary sphincter muscle and restored urinary sphincter function after a single dose of treatment. Versameb plans to launch a Phase 2a open label, first-in-human dose ascending study of VMB-100 in female subjects with moderate stress urinary incontinence in the first half of 2024.

About Stress Urinary Incontinence
Stress urinary incontinence is a common condition amongst women in which a leakage of urine occurs during moments of physical activity due to a weakened urinary sphincter muscle. SUI is the most common type of urinary incontinence, affecting 86% of incontinent women. Despite the prevalence of SUI, there are currently no approved pharmacological therapies available in the United States. Current standard of care protocol includes short-term solutions like pelvic floor therapy or a highly invasive surgical procedure in which a sling is permanently implanted into the urethra or bladder neck.