Current diagnostic standards for Autism which also serve as a basis for drug development in the field are solely based on behavioral manifestations and fail to acknowledge the genetic and biological diversity encompassed in the word “Autism” leaving many patients without effective treatment options.
STALICLA is taking a different approach defining the molecular and biological basis for subgroups of patients with Autism and other Neurodevelopmental disorders (NDDs) (such as schizophrenia or dyspraxia…) starting with patient information before developing drugs. To do this, the company’s researchers have developed computational models that specifically tackle the challenges associated with breaking-up into biological subgroups of ill-defined conditions such as Autism.
STALICLA’s computational models enable to link many levels of information with one another - for instance genetic, biological and medical history - to identify common biological routes that are disrupted in some patients and identify tailored medicine to target them.
STALICLA’s approach also opens the possibility to advance precision treatment options for patients with Autism and NDDs with no clear genetic cause, based on biological underpinnings. This is important as these patients represent the majority of patients diagnosed with Autism!
This mission is only made possible through close collaboration with patients, families and physicians who share our team’s dedication to finding novel treatments for patients with Autism and other NDDs who feel impaired by their symptoms.
STALICLA’s first development product is STP1 and addresses the distinct subgroup of ASD-Phen1 patients. STP1 had entered a clinical Phase 1b trial in December 2020. This randomized, double-blind, placebo-controlled, first-in-human clinical study is conducted at Cincinnati Children’s Hospital Medical Center in Cincinnati, Ohio, USA. The trial has been designed to evaluate the safety and tolerability of a two-week oral treatment with STP1 in adult patients who match the ASD-Phen1 clinical criteria. The study will also assess the pharmacokinetic and pharmacodynamic effects of STP1 and include exploratory efficacy endpoints.
Autism is known as a “spectrum disorder” because of its wide heterogeneity in cause, manifestation and severity. It can involve a wide range of symptoms; it can be relatively minor for some or a disability that needs full-time care for others. This marked heterogeneity of the condition clearly suggests that there is no “autism” but “autisms” that include multiple causes and distinct biological groups. Recognizing this diversity could revolutionize autism treatment.
There is currently no available treatment to address the core symptoms of autism. And the development of new drugs that truly serve patients has so far been proceeding slowly. Multiple clinical studies have highlighted the heterogeneity of patients with regards to treatment response, typically resulting in just a subset of the patients improving under treatment. These findings support the need to identify subgroups of subjects with autism who might respond to an appropriate treatment.
STALICLA leverages on its proprietary drug-discovery platform to bring personalized medicine to patients with autism and other ill-defined NDDs. This platform is called called DEPI: Databased Endophenotyping Patient Identification. DEPI analyses vast amounts of anonymized data from large cohorts of patients with ASD, including clinical data, genetic data, and other complex biological data. By identifying patterns and links in this information, DEPI can help differentiate the patients into more-homogeneous subgroups.
This is the first step away from a one-size-fits-all approach, and towards personalized treatment options for patients who feel impaired by the symptoms of their condition.
ASD Phenotype 1 (ASD-Phen1) is a subgroup of patients with autism (Autism Spectrum Disorder, ASD), which has been identified by STALICLA’s platform, based on large clinical and laboratory datasets. ASD-Phen1 was validated by an observational clinical trial conducted at the Greenwood Genetic Center (SC, U.S.). ASD-Phen1 criteria were applied to a cohort of 313 patients with autism and a further subgroup of 90 patients. This study led to the identification of patients who matched the required clinical criteria and represented the first clinical validation of the ASD-Phen1 subgroup. Further biological characterization of ASD-Phen1 revealed a specific biological signature for this patient subgroup. ASD-Phen1 could include up to 25% of the total ASD population with a non-monogenetic cause. The co-occurrence of a specific set of clinical signs and symptoms allows the identification of patients with ASD-Phen1.
STP1 is the first precision medicine being developed for the treatment of ASD in patients within the Phenotype 1 subgroup (ASD-Phen1). STP1 is a novel combination of a phosphodiesterase (PDE) inhibitor with anti-inflammatory properties and a modulator of synaptic excitatory/inhibitory activity. This combination is assessed for its capacity to target molecular pathways that appear to be dysregulated in patients with ASD-Phen1.
While this combination is novel, there have been extensive research conducted in animal models and humans with the individual components of STP1, one of them already being approved by the US FDA for another indication than autism. The individual compounds comprising STP1 were proven to be safe in animals and in humans. Given its safety profile and treatment potential, the Food and Drug Administration (FDA) agency has recently approved STP1 to be investigated for safety and efficacy in patients with ASD-Phen1.
STALICLA is conducting observational clinical studies in collaboration with leading medical universities and research centers to further validate patient subgroups (phenotypes) and then identify which investigational clinical trials patients belonging to these subgroups may benefit from.