BIO Asia–Taiwan 2022 亞洲生技大會

BIO Asia–Taiwan 2022 亞洲生技大會

講師

Klaas Zuideveld

Session 5 – New Modalities to Cure

Date:27 July (Wednesday)
Time:  15:40 – 17:10 (GMT+8)

Klaas Zuideveld

CEO
Versameb AG

Dr. Klaas Zuideveld brings over 20 years of drug development and life science industry experience to Versameb at a pivotal stage in the Company’s development as two of its lead assets transition from early discovery into clinical development. Klaas joined Versameb as Chief Development Officer in May 2020. Prior to this, Klaas has held leadership positions at Roche where amongst other things he has led the clinical development of Avastin™ (bevacizumab), and at Caris Life Sciences where he was responsible for the company’s first companion diagnostic partnership in oncology. He has further worked for and advised Mosaic Biomedicals (acquired by Northern Biologic), T3 Pharma, Envision Sciences, Therachon (acquired by Pfizer) and Nucleai.
 

Speech title & Synopsis

Regeneration of urethral muscle in Stress Urinary Incontinence using engineered mRNA

The essential role of Insulin-like growth factor-I (IGF-I) in activating stem cell processes during skeletal muscle development, homeostasis and regeneration after trauma has been extensively investigated and provides a huge therapeutic potential for IGF-I in those conditions. Its clinical relevance has been shown in multiple diseases including growth disorders, diabetes, neurological diseases, and musculoskeletal regeneration in multiple clinical trials. However, market approval has only been granted in genetic IGF-I deficiency due to side effects upon systemic application. 
We generated an engineered IGF-I-encoding mRNA through our VERSagile platform to enhance protein secretion. IGF-I protein expressed upon mRNA uptake was fully functional in vitro and in vivo. Its regenerative potential after local injection was tested in three animal models of physical and myotoxic injury as well as stress urinary incontinence (SUI). After myotoxic injury, the optimized IGF-I mRNA showed a much higher potency than non-optimized mRNA in accelerating full recovery of muscle function and structure after early intervention, providing in vivo confirmation of the optimization. In a physical injury model, a single intramuscular injection of optimized IGF-I mRNA exhibited a robust pharmacokinetic mRNA profile inducing local IGF-I expression and secretion that activated downstream mechanisms enhancing stem cell recruitment required for muscle regeneration. In the SUI model, a single intraurethral injection of optimized IGF-I mRNA showed full recovery of urinary continence and structural regeneration of urethral tissue.
The data show that local IGF-I mRNA injection results in therapeutically relevant IGF-I protein expression and secretion in muscle tissue. Consequently, activation of downstream processes of muscle regeneration created functional and structural benefit preventing tissue damage and accelerating recovery in three different paradigms of muscle insults. The strong effects seen even after a single local injection support its therapeutic potential in muscle-related disorders such as stress urinary incontinence.