TDXD is highly emetogenic. Adding low-dose olanzapine to the standard three-drug antiemetic prophylaxis regimen is a transformative strategy that significantly reduces both acute and delayed nausea, making the potent therapy much more tolerable for patients.

Instead of a traditional biomarker-first approach, Alto took a drug already approved in Europe (agomelatine) and used machine learning on patient EEG data to discover a novel biomarker that predicts who responds best. This "reverse-engineering" approach de-risks development by finding a precise population for a proven drug.

Autobahn Therapeutics avoids the high failure rate of novel CNS targets. Instead, their strategy combines a biologically validated mechanism (thyroid hormone's effect on depression) with a proprietary prodrug platform that solves its historical limitation—peripheral side effects. This creates a rare combination of a de-risked target and strong IP.

Instead of relying on finding novel targets, a key strategy in neuropsychiatry is to revisit failed compounds that showed efficacy signals. Companies use modern chemistry and delivery to engineer solutions that separate efficacy from the historical liabilities that halted development, turning past failures into new opportunities.

French startup Elk Edonia is developing a first-in-class depression therapy targeting the intracellular transcription factor Elk One. Unlike traditional antidepressants acting on extracellular synapses, this small molecule modulates gene expression related to neuroplasticity and inflammation, aiming to make depression an acute, treatable condition rather than a chronic one.

Neurocrine's strategy with its M4 agonist hinges on achieving superior safety and tolerability through high selectivity. The company believes that for chronic psychiatric disorders, long-term patient adherence—driven by fewer side effects—is a more critical factor for commercial success than marginal gains in efficacy.

Autobahn Therapeutics focuses on atypical depression, a patient subtype characterized by overeating and oversleeping, colloquially called "sleeper eaters" by psychiatrists. This defined group represents about a third of Major Depressive Disorder patients but has no approved medications, creating a clear unmet need and a targeted regulatory pathway.

For nausea associated with the ADC TDXD, clinicians find adding low-dose olanzapine (2.5mg at bedtime) is a highly effective strategy for both acute and delayed nausea. This practical tip improves tolerability beyond standard three-drug prophylaxis.

To maximize market reach, Alto Neuro is simultaneously developing its lead drug as an add-on therapy for psychiatrists and as a standalone monotherapy for primary care physicians. This dual strategy caters to different prescriber behaviors and aims for broader, faster adoption upon approval by serving the full spectrum of patients and doctors.