Novel PDA10A Inhibitor for Schizophrenia in Development, Discussion With Maciej Wieczorek, MD

In an exclusive interview with Psychiatric Times, Maciej Wieczorek, PhD CEO of Celon Pharma, discussed the development of CPL36, a novel phosphodiesterase 10A (PDE10A) inhibitor being investigated for schizophrenia. Wieczorek emphasized that CPL36 represents a new mechanism of action distinct from existing antipsychotics, which primarily act through dopamine D2 receptor blocking. PDE10A is highly expressed in the striatum—an area implicated in psychosis—allowing CPL36 to modulate dopaminergic signaling selectively by rebalancing the indirect pathway rather than blocking dopamine receptors directly. This targeted approach is expected to minimize extrapyramidal and metabolic side effects commonly associated with both first-generation and atypical antipsychotics.

Preclinical and early clinical data have demonstrated promising efficacy and safety.¹ In a phase 2 trial involving patients with schizophrenia, CPL36 produced statistically significant and clinically meaningful symptom improvement after only 4 weeks of treatment, without evidence of weight gain, dyslipidemia, or glucose impairment. These findings suggest potential advantages in long-term cardiovascular and metabolic outcomes.

Wieczorek noted that CPL36’s development benefited from over a decade of medicinal chemistry efforts to achieve favorable pharmacodynamic properties, including a fast dissociation rate from the enzyme, which may underlie its clinical efficacy. Celon Pharma plans to initiate a phase 3 program comparing CPL36 directly with olanzapine.² Key endpoints will include efficacy and metabolic outcomes. Wieczorek expressed optimism that CPL36 could offer a major advance for patients who do not respond adequately to current therapies while avoiding their most common side effects.

References

1. Kumar M. Celon Pharma’s CPL’36 yields positive results in Phase 2 schizophrenia trial. World Pharmaceutical Frontiers. July 10, 2025. Accessed October 24, 2025. https://www.worldpharmaceuticals.net/news/celon-pharmas-cpl36-yields-positive-results-in-phase-2-schizophrenia-trial/

2. FDA clears Celon Pharma's novel PDE10A inhibitor CPL-936 for phase 3 schizophrenia trials. MedPath. October 8, 2025. Accessed October 24, 2025. https://trial.medpath.com/news/30fafbf057350363/fda-clears-celon-pharma-s-novel-pde10a-inhibitor-cpl-936-for-phase-3-schizophrenia-trials