Periodic Reporting for period 1 - NeuroPa (Targeting the brain sigma-1 receptor: A paradigm shift for the treatment of neuro-degenerative disorders) Reporting period: 2019-12-01 to 2020-05-31 Summary of the context and overall objectives of the project We are developing igmesine, a proprietary drug that holds the potential to provide treatment for almost all neurodegenerative diseases (NDD's: ALS, AD & PD are currently prioritized due to favorable development timelines), by successfully targeting multiple critical molecular processes involved in neurodegeneration. Igmesine activates, with high potency and specificity, recently characterized Sigma-1 receptors (Sigma-1R). The receptors are highly expressed in neurons and supporting cells (glia) of the central nervous system. Activation of Sigma-1R prevents cell-death, calcium excitotoxicity, accumulation of toxic misfolded proteins, limits oxidative stress and neuroinflammation. Intervention in these processes represents a novel, par excellence approach to slow down the progression of multiple neurogenerative disorders. SigmaThera designed the NeuroPa project to get a clear understanding of the commercial potential of igmesine, to strengthen their clinical development strategy and to define their optimal business strategy. The following report contains the market analysis, clinical & regulatory feasibility, and commercial feasibility. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The objectives of the Neuropa project were intended to maximize the chance of igmesine, and with it SigmaThera, becoming a success. This included a market analysis to assess the attractiveness and the dynamics of the target market of neurodegenerative diseases and define the most optimal commercialization strategy based on clinical development pathways and IP strategies. There are significant pipeline competitors for igmesine in all target markets within the neurodegenerative market. This is driven by the large unmet needs caused by the lack of curative treatments. Although ALS currently holds the smallest market in terms of size and number of diagnosed patients, the commercial feasibility remains the highest due to the favourable clinical development pathway. Because of the rarity of the disease and high unmet need orphan drug designation status is expected to be granted. This would drastically shorten the clinical development timelines. In addition, due to the rapid disease progression, outcome measurements will be favourable for ALS compared to other NDD’s further adding to the commercial feasibility for igmesine. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) Initially we will clinically validate Igmesine for the use against ALS. Although ALS currently holds the smallest market in terms of size and number of diagnosed patients, the commercial feasibility remains the highest due to the favourable clinical development pathway. Because of the rarity of the disease and high unmet need Orphan Drug Designation status is expected to be granted. This would drastically shorten the clinical development timelines. In addition, due to the rapid disease progression, outcome measurements will be favourable for ALS compared to other NDD’s further adding to the commercial feasibility for Igmesine. Upon successfully receiving market authorization for ALS, we will seek out a licensing deal with a large pharmaceutical industry partner to commercialize Igmesine. The generated funds from this deal will be invested in further development of our therapeutic pipeline by initiating clinical validation against AD followed by other neurodegenerative diseases alike. This strategy will ensure that the maximum number of patients with varying neurodegenerative diseases will ultimately benefit from igmesine. sit-ec.png
