Reflections from SIRS 2026: Addressing Cognitive Impairment in Schizophrenia

Cognitive deficits are a core feature of schizophrenia and a primary driver of disability for most of the 24 million people living with the disease. Despite its profound impact on daily functioning and independence, cognitive impairment associated with schizophrenia (CIAS) still has no approved therapies.

At this year’s Schizophrenia International Research Society Congress, that gap was illuminated across many presentations and discussions.

For decades, the clinical management of schizophrenia has been marked by meaningful progress in treating psychosis, but minimal progress has been made to address one of the most debilitating aspects of the disease – cognitive impairment.

Encouragingly, I think we are beginning to see a shift in both attention and focus on addressing cognition. We were proud to be part of those discussions, sharing positive topline results from our Phase 1 study of KYN-5356 in healthy volunteers at the conference.

Why Addressing Cognition Requires a Different Approach

Kynurenic acid (KYNA) levels have been shown to be elevated in schizophrenia and are believed to be a key driver for not only CIAS but also other disorders affecting cognition, such as Alzheimer’s. This biology points directly to the kynurenine pathway, and specifically to KAT-II, the enzyme responsible for the production of KYNA.

KYN-5356 is our potential first-in-class, highly selective KAT-II inhibitor, designed to lower KYNA in the brain and improve cognition. Importantly, our strategy is rooted in human biology, integrating genetics, translational biomarkers, and clinical data to validate both the mechanism and the patients most likely to benefit from this therapy. This foundation is what gave us confidence heading into the clinic, and what makes our Phase 1 results particularly meaningful, including:

• Favorable safety and tolerability, reaching therapeutic concentrations in plasma and cerebrospinal fluid (CSF)
• Biochemical target engagement, with KYN-5356 showing a dose-dependent reduction of KYNA levels in the CSF while increasing the CSF glutamate/glutamine ratio
• Enhanced brain activity associated with cognition, leading to improved cognitive performance

While our study was not powered for efficacy, the exploratory pharmacodynamic (PD) endpoints suggested early evidence of benefit for cognitive improvement, an important finding in a field for an indication that so far has been elusive. These results give us confidence that we are engaging a biologically relevant pathway in a way that could translate into clinical benefit for people living with CIAS and beyond.

You can see the oral presentation here.

Looking Ahead

The discussions at SIRS reinforced both the urgency of the problem and the opportunity ahead. There is growing recognition that improving cognition is essential to improving people’s lives, and that belief is what drives our work.

Ultimately, our success won’t be defined by target engagement or favorable safety and tolerability alone, but by being able to deliver improvements in cognition for patients.

As we look ahead to our anticipated Phase 2 readout of KYN-5356 in CIAS later this year, and to advancing our program into Alzheimer’s disease, we remain focused on what matters most: translating this innovative approach into real impact for people living with cognitive impairment.