Kynexis, a Dutch biotech, has raised €97 million ($113 million) to advance a drug aimed at one of psychiatry’s most stubborn problems: the cognitive symptoms of schizophrenia.
The extended Series A will fund KYN-5356, a KAT-II inhibitor designed to restore balance in brain receptors involved in learning, memory and executive function. The round was backed by Novartis’s venture arm and Forbion.
The symptoms nobody treats
Schizophrenia is popularly identified with hallucinations and delusions — the positive symptoms — and those are what antipsychotic drugs address, generally with reasonable success.
They are not what determines how patients live. Cognitive impairment associated with schizophrenia (CIAS) affects an estimated 80% of people with the condition and involves difficulties with working memory, attention, processing speed and executive function — the capacities required to hold a job, manage finances, maintain relationships and live independently.
Functional outcome in schizophrenia correlates far more closely with cognitive impairment than with positive symptoms. A patient whose hallucinations are well controlled but who cannot sustain attention or plan a sequence of tasks remains substantially disabled, and no therapy is specifically approved for that.
Why it has been a graveyard
CIAS has defeated a long succession of drug developers, and the reasons are instructive.
The biology is poorly defined. Cognitive impairment in schizophrenia is not obviously a deficiency of one neurotransmitter, and candidate mechanisms have spanned dopamine, glutamate, acetylcholine and others without any single one accounting for it.
Measurement is also difficult. Cognitive test batteries are lengthy, subject to practice effects across repeated administration, and their relationship to real-world functioning is imperfect — so a drug can improve test scores without changing anything patients notice, and regulators have been appropriately sceptical of that.
Add the fact that patients are already taking antipsychotics, some of which impair cognition themselves, and the signal a new drug must produce is buried under considerable noise.
What KAT-II inhibition does
The mechanism runs through the kynurenine pathway, which metabolises the amino acid tryptophan. One product of that pathway, kynurenic acid, is an antagonist at receptors central to learning and memory — and elevated levels have been reported in schizophrenia.
KAT-II is the enzyme producing kynurenic acid in the brain. Inhibiting it lowers kynurenic acid, which should reduce the blockade on those receptors and restore signalling toward normal.
The logic is appealingly direct: an endogenous molecule is present in excess and is inhibiting the exact receptors relevant to the impaired functions, so reduce it. Whether the excess is a cause of the impairment or a marker accompanying it is the question the trial exists to answer.
Where the drug stands
KYN-5356 is in a Phase 2 proof-of-concept trial enrolling about 150 adults across 13 US sites, with topline results expected by the end of 2026 and a registrational trial planned.
Funds will also support closing out the Phase 2, preparing the next trial, and exploring the drug in other cognitive disorders including Alzheimer’s.
Why the Alzheimer’s mention is strategically significant
Extending a cognitive-enhancement mechanism into Alzheimer’s is a common ambition and a reasonable one here, because the kynurenine pathway has been implicated in neurodegeneration as well as psychiatric illness.
It also changes the commercial calculation substantially. A drug for CIAS addresses a defined population within schizophrenia; the same mechanism working across cognitive disorders addresses a far larger one. Investors funding a Phase 2 in a graveyard indication are generally buying the platform possibility alongside the immediate one.
Why the funding is notable
€97 million into an indication with a documented history of failure, from investors including a major pharmaceutical company’s venture arm, indicates the mechanism was found persuasive rather than the disease area being fashionable.
Corporate venture participation is a particular signal, since those arms are staffed by people who evaluate such mechanisms professionally and whose parent company would be a plausible acquirer if the readout is positive.
What the readout has to show
A Phase 2 in about 150 patients can demonstrate an effect on cognitive testing. What will determine whether the programme proceeds credibly is whether that effect is large enough to matter functionally, and whether it appears on measures regulators accept.
Why the antipsychotic era left this gap
The neglect of cognitive symptoms is partly historical, and understanding why explains the size of the opportunity.
Antipsychotics were discovered by accident in the 1950s and worked on positive symptoms, so those became the definition of treating schizophrenia. Regulatory pathways, rating scales and clinical practice all organised around measuring hallucinations and delusions, because those were what the available drugs changed.
Cognitive and negative symptoms were recognised throughout and stayed peripheral, in part because no treatment addressed them and in part because they are harder to measure. A patient reporting fewer voices is straightforward to score; a patient whose working memory has improved enough to hold a job is not.
The consequence is a treatment landscape optimised for the symptoms drugs happened to affect rather than the ones determining outcomes — and a regulatory path for cognitive endpoints that had to be constructed relatively recently, which is part of why so many programmes stumbled on endpoint selection rather than on biology.
The field’s history is full of compounds producing statistically significant improvements on cognitive batteries that translated into nothing patients or families could perceive. A meaningful result would need to move both a cognitive measure and a functional one in the same direction. Business news, not investment advice.