The numbers behind autism spectrum disorder are staggering. According to the CDC, one in 44 American children is impacted by autism spectrum disorder (ASD) — but today’s treatments provide little relief. Drugs such as antipsychotics or antidepressants can help manage certain symptoms such as irritability or repetitive behaviors, yet no treatments have emerged that target the core of the disease.
Part of the challenge is that ASD is not one condition but many, each with different underlying factors, said Lynn Durham, founder and CEO of Stalicla, a Swiss clinical stage biotech developing precision therapeutics for ASD and other neurodevelopment disorders. In fact, as many as 100 different gene variants may play a role in ASD risk.
“One of the things that you know when you see hundreds of people with autism is that when you've seen one person with autism, you've seen one person with autism,” Durham said.
This is why the company is banking on a precision medicine approach to the disorder. With the help of its AI-driven discovery platform called Databased Endophenotyping Patient Identification, or DEPI, Stalicla can sort ASD patients into subtypes and develop therapeutic drugs tailored to each group.
So far, the results of this approach have been trending in the right direction. Last spring Stalicla announced the successful completion of phase 1b trials for its lead candidate, STP1, a combo therapy that contains a PDE inhibitor and an NKCC1 inhibitor. The therapy targets a subgroup called ASD phenotype 1, which makes up some 20% of ASD cases. In the trial, STP1 not only hit its safety targets, but showed promise in improving important neurological and behavioral clinical measures.
“We have the first clinical efficacy results on our pipeline, showing the strongest target engagement data that has ever been reported in the field,” Durham said. The drug will now move into phase 2.
Stalicla also has a second candidate called STP2 heading into phase 2 trials. It’s designed to treat a second subgroup, ASD phenotype 2, which comprises 15% to 20% of ASD cases. Also in the pipeline are drugs for three additional ASD phenotypes, 3, 5 and 6, which Stalicla is pursuing through third-party partnership agreements.
Here, Durham discusses a potential timeline for its drug development aims and why she has zeroed in on creating new treatments for ASD.
This interview has been edited for style and brevity.
PHARMAVOICE: Why did Stalicla set out with a focus on autism?
LYNN DURHAM: I have a life-long involvement with the neurodevelopmental disorder community. Both my brother and son have autism. And I wanted to make a change in the field and shift the field away from behaviorally defined indications that don't offer any, or offer very little insight into the underlying genetic and molecular theology of the disease to be able to start stratifying patients and enabling the advancement of precision medicine in the field.
What is your overall goal for Stalicla?
We want the company to prove the feasibility of precision medicine for neurodevelopmental and neuropsychiatric disorders. The company is built on a mission to enable the advancement and the standardization of precision medicine for patients with neurodevelopmental disorders and neuropsychiatric disorders. Today, neuropsychiatry is the least evidence-based discipline in medicine and this needs to change because the brain is profoundly biological and there's no reason not to apply biologically driven treatment strategies for these populations.
Can you tell me a little bit about the technology that you’re using?
We are integrating multiple sets of data, beyond behavioral data. So obviously, genetic (data). But also, other types of omics data, as well as electronic health record-related data, for example, comorbidities that have a convergence in terms of the underlying genes and pathways that are involved, and a family disease history. The whole idea here is to take a systems biology approach to autism, considering the genes and molecular pathways that are involved in the development and the functioning of the CNS (central nervous system) are also involved in other organs and diseases. So, we're talking about systems diseases, rather than pure brain diseases.
How will patients eventually know that they’re in one of the categories that might be helped by the drugs that you are working on?
We are not only developing a drug, we're developing biomarkers to be able to bring them into companion diagnostics. So that one day, instead of recruiting patients on biologically supported phenotypes, we will recruit patients on the basis of blood-based biomarkers. Just like we do for breast cancer.
Can you tell me some more about your research findings to date?
The most advanced clinical trials that we have were in the phase 1b on the STP1 asset. We found extremely strong target engagement measured by EEG (electroencephalography) and ERP (event-related potentials) in specific areas of the brain related to social interaction and executive function. And we know, for instance, that the changes in processing speed, which we measured as an effect of STP1 treatment, are the earliest predictors of changes in social communication endpoints. That was measured previously in behavioral intervention.
Did patients in the studies note any differences in behavior or social interactions?
It's difficult, because phenotype1 patients are mild-to-moderate, severely affected patients. The mean IQ for phenotype 1 patients is 65. So, their self-awareness about the treatment is limited. But we're very much focused on choosing endpoints that are not overly influenced by placebo (so) we integrated computerized panels (and) computerized boxes as outcome measures. One of them is called the NIH toolbox and it's a computerized measurement. It's absolutely quantifiable and it's not subject to placebo. So, what we're seeing are early changes in sub items of cognition, such as processing speed (and) reaction time, that are building bricks to larger scale change, which will result hopefully in changes in social communication end points.
What is the potential timeline for when people might have access to these medications?
For STP1, we're talking about 2027. For STP2, we're talking about 2028. And for subsequent assets, or at least future assets, we're also talking about 2027. This (STP1) phase 1b has been really a pivotal moment for Stalicla because it allowed us to mature our pipeline profile and to increase the probability that these products will get to market.
Why do you think creating treatments for ASD is so important?
I think that neuropsychiatric disorders are a pressing societal issue, because we're not addressing them in a biologically driven manner, and because when someone's brain is not functioning, that puts individuals in a very weak position in terms of their self-determination, dignity and safety. And that is our role. We have to address this as a society, and it will have major impact on us as a society to be able to support people in the functioning of their brains to bring more dignity and self-determination. So, it's a major ethical and societal and economic issue.