Precision medicine for treatment of absence seizures with highly differentiated pharmacology
SAN711 is a first-in-class positive allosteric modulator of GABAA a3 receptors in development for treatment of absence seizures (childhood absence seizures/juvenile absence seizures). SAN711 is specifically designed to suppress the electroencephalographic manifestations of an absence seizure, the Spike-Wave-Discharges (SWDs), targeting the root cause of the pathophysiology without having any detrimental effects on cognition.
How SAN711 works
Typical EEG recordings from GAERS rats injected systemically with vehicle or the indicated doses of SAN711. Enlarged sections are indicated below each trace.
Crunelli V et al., Selective activation of alpha 3-containing GABA-A receptors blocks absence seizures and increases sleep spindles. Society for Neuroscience annual meeting, Washington D.C., November 11-15, 2023. Poster no. 526.08
SAN711 is a Positive Allosteric Modulator, or PAM, of GABAA α3 containing receptors. GABA is a neurotransmitter, that mediates inhibitory electrical signals between nerve cells in the brain. GABAA is the target of the non-selective and highly effective medicines belonging to the chemical group referred to as “benzodiazepines”. Unlike benzodiazepines, SAN711 does not have an impact on GABAA α1, α2 and α5 subunits, thus being devoid of the sedation, motor instability, abuse liability, and memory impairing effects that limit the use and tolerability of benzodiazepines.
Absence seizures are caused by short bursts of uncontrolled electrical activity in specific neuronal circuits in the brain. During an absence seizure, the patient is unresponsive and has impaired consciousness, typically observed as “staring spells”. Absence seizures normally last a few seconds (usually less than 15 seconds) and can occur up to 200 times a day. Absence seizures occur in multiple genetic generalized epilepsies, including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), and juvenile myoclonic epilepsy (JME).
Saniona has specifically designed SAN711 to enhance the effect of the α3 containing GABAA receptors with high selectivity.
The α3 subunit is highly expressed in parts of the brain that are critically involved in initiation and maintenance of absence seizures. By selectively enhancing the effect of GABA at α3 GABAA receptors, the Company believes that SAN711 is a precision approach for specific abortion of absence seizures while avoiding the adverse effects associated with the current first line therapy such as impaired cognition.
Preclinical data generated in a highly translatable rodent model for absence seizures (Genetic Absence Epilepsy Rat from Strasbourg, GAERS), confirms marked suppression of absence seizures.
SAN711 has successfully finalized a Phase 1 study confirming favorable human pharmacokinetics and excellent tolerability at maximal receptor occupancy.