Promising molecules for the treatment of cognitive impairments A company created in early 2018, Syndesi Therapeutics is benefiting from over 15 years of research at UCB which identified novel modulators of SV2A that show pro-cognitive properties in preclinical models. Its goal is to demonstrate the potential of these molecules to reduce the symptoms of cognitive impairment in patients with Alzheimer’s Disease and related conditions.
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t all goes back to 2004: this was when UCB identified the synaptic vesicle protein, SV2A, as the target for its anti-epileptic drug, levetiracetam (Keppra®). This discovery enabled UCB to develop a second anti-epileptic drug that modulates SV2A, brivaracetam (Briviact®).
ubiquitous pre-synaptic mechanism rather than a specific neurotransmitter and modulates a clinically precedented target. Modulation of synaptic transmission is relevant since there is increasing evidence that in multiple CNS disorders cognitive impairment is correlated with a loss of synapses resulting in a loss of connectivity in the brain. Positive modulation of SV2A by SDI-118 could mitigate this loss of connectivity by increasing the efficiency of remaining synapses. In addition, Syndesi has been able to leverage a PET ligand for SV2A (11C-UCB-J), developed by UCB, which enables direct measurement of SV2A occupancy by SDI-118 in the human brain. This is a major de-risking factor for CNS drug development.
© Syndesi Therapeutics
During the course of UCB’s research program on SV2A, UCB discovered a different class of SV2A modulators that show pro-cognitive but not anti-epileptic properties in preclinical models. This is where Syndesi comes into play: the company has an exclusive license to these Dr Jonathan Savidge, pro-cognitive SV2A modulator molecules, and CEO of Syndesi Therapeutics has conducted research to further characterise their mechanism of action. It is backed by a strong syndicate of Belgian and international investors (Novo (Denmark), Fountain Healthcare (Dublin), the corporate venture Syndesi successfully completed Phase I enabling studies in 2018 fund Johnson & Johnson Innovation - JJDC, V-Bio, SRIW, Vives), and conducted a first-in-human, single-dose Phase I study with together with stakeholder UCB and continued support for the SDI-118 in 2019. The Phase I study included imaging of brain programme from the Walloon Region. Since it started operaSV2A occupancy with SDI-118 using the 11C-UCB-J PET ligand. The company is currently conducting a second Phase I multiple tions Syndesi Therapeutics has raised €23M from these six indose study to investigate safety, tolerability and pharmacokinetics vestors and UCB, and was awarded a recoverable loan from of SDI-118 over 14 days dosing. It also anticipates starting Phase the Walloon Region of up to €3.2 M. Ib/IIa exploratory studies to investigate the effects of SDI-118 on cognition during Q1 2021. This is good news since Alzheimer’s Disease International estimates that there are 50 million people with dementia worldwide. According to WHO, there are also 20 million people worldwide suffering with schizophrenia and 80% of them have cognitive impairment. And that’s not all: WHO also estimates there are 264 million people worldwide suffering from depression, around 20% of whom also suffering from cognitive impairment. Syndesi’s SDI-118 could, therefore, address additional major unmet medical needs given that there are no approved therapies for cognitive impairment associated with schizophrenia and depression.
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Syndesi Therapeutics
Syndesi is focussed on the development of orally active small molecules with a lead compound, designated SDI-118, now in Phase I clinical development, which is targeting central nervous system (CNS) disorders where patients suffer from cognitive impairment, such as; Alzheimer’s Disease, other dementias, schizophrenia, and depression. Its approach directly targets a
Syndesi Therapeutics SA Centre d’Entreprises et d’Innovation (CEI) Incubator Chemin du Cyclotron 6 - 1348 Louvain-la-Neuve Tel.: +32 (0)10 280 238 Email: info@syndesitherapeutics.com https://www.syndesitherapeutics.com/ 162
