Alto Neuroscience Announces Data Presented at the 63rd Annual Meeting of the American College of Neuropsychopharmacology
Alto Neuroscience (NYSE: ANRO) presented multiple studies at the 63rd ACNP annual meeting, showcasing progress in their precision psychiatry platform. The company highlighted new mechanistic findings supporting the ALTO-300 biomarker, which measures reduced neural signal stability and is linked to 5-HT2C receptor activity.
Key presentations included data on neural mechanisms of the ALTO-300 biomarker, validation of reward processing assessments for ALTO-203 trials, and findings on cognitive impairment in depression. The company announced plans for an interim analysis of the ongoing ALTO-300 Phase 2b trial in Q1 2025, with complete topline data expected in H1 2025.
Alto Neuroscience (NYSE: ANRO) ha presentato numerosi studi al 63° congresso annuale dell'ACNP, mostrando progressi nella loro piattaforma di psichiatria di precisione. L'azienda ha messo in evidenza nuove scoperte meccaniche a supporto del biomarker ALTO-300, che misura la stabilità ridotta del segnale neurale ed è collegato all'attività del recettore 5-HT2C.
Le presentazioni chiave hanno incluso dati sui meccanismi neurali del biomarker ALTO-300, la validazione delle valutazioni del processamento della ricompensa per i trial ALTO-203, e i risultati sull'impatto cognitivo nella depressione. L'azienda ha annunciato piani per un analisi intermedia del trial ALTO-300 di fase 2b in Q1 2025, con dati completi attesi nel primo semestre del 2025.
Alto Neuroscience (NYSE: ANRO) presentó múltiples estudios en la 63ª reunión anual de la ACNP, mostrando avances en su plataforma de psiquiatría de precisión. La compañía destacó nuevos hallazgos mecánicos que respaldan el biomarcador ALTO-300, que mide la reducción de la estabilidad de la señal neural y está relacionado con la actividad del receptor 5-HT2C.
Las principales presentaciones incluyeron datos sobre los mecanismos neuronales del biomarcador ALTO-300, la validación de las evaluaciones del procesamiento de recompensas para los ensayos ALTO-203, y hallazgos sobre el deterioro cognitivo en la depresión. La compañía anunció planes para un análisis intermedio del ensayo ALTO-300 de fase 2b en el primer trimestre de 2025, con datos completos esperados en la primera mitad de 2025.
알토 뉴로사이언스 (NYSE: ANRO)는 제63회 ACNP 연례 회의에서 여러 연구 결과를 발표하며 정밀 정신의학 플랫폼의 발전을 보여주었습니다. 이 회사는 신경 신호 안정성 감소를 측정하고 5-HT2C 수용체 활동과 관련된 ALTO-300 바이오마커를 뒷받침하는 새로운 기전 발견을 강조했습니다.
주요 발표에는 ALTO-300 바이오마커의 신경 메커니즘에 대한 데이터, ALTO-203 시험을 위한 보상 처리 평가의 검증 및 우울증에서의 인지 impairment에 대한 발견이 포함되었습니다. 이 회사는 2025년 1분기에 진행 중인 ALTO-300 2b 단계 시험의 중간 분석 계획을 발표했으며, 전체 주요 데이터는 2025년 상반기에 예상됩니다.
Alto Neuroscience (NYSE: ANRO) a présenté plusieurs études lors de la 63e réunion annuelle de l'ACNP, mettant en avant les avancées de sa plateforme de psychiatrie de précision. L'entreprise a souligné de nouvelles découvertes mécaniques soutenant le biomarqueur ALTO-300, qui mesure la stabilité réduite des signaux neuronaux et est lié à l'activité du récepteur 5-HT2C.
Les présentations clés comprenaient des données sur les mécanismes neuronaux du biomarqueur ALTO-300, la validation des évaluations du traitement des récompenses pour les essais ALTO-203, et des résultats sur les déficits cognitifs dans la dépression. L'entreprise a annoncé des plans pour une analyse intermédiaire de l'essai ALTO-300 de phase 2b au premier trimestre 2025, avec des données clés complètes attendues au cours du premier semestre 2025.
Alto Neuroscience (NYSE: ANRO) präsentierte mehrere Studien auf dem 63. jährlichen Treffen der ACNP und zeigte Fortschritte in ihrer Plattform für Präzisionspsychiatrie. Das Unternehmen hob neue mechanistische Erkenntnisse hervor, die den ALTO-300 Biomarker unterstützen, welcher die reduzierte Stabilität neuronaler Signale misst und mit der Aktivität des 5-HT2C Rezeptors verbunden ist.
Wichtige Präsentationen beinhalteten Daten zu den neuronalen Mechanismen des ALTO-300 Biomarkers, die Validierung von Belohnungsbearbeitungsbewertungen für die ALTO-203 Studien und Ergebnisse zu kognitiven Beeinträchtigungen bei Depressionen. Das Unternehmen gab Pläne für eine interim Analyse der laufenden ALTO-300 Phase 2b Studie im ersten Quartal 2025 bekannt, mit vollständigen Topline-Daten, die in der ersten Jahreshälfte 2025 erwartet werden.
- Preclinical data validates ALTO-300's biomarker mechanism, strengthening the scientific basis for ongoing trials
- Development of improved reward processing assessment tools for ALTO-203 clinical trials
- Clear timeline for ALTO-300 Phase 2b trial results with interim analysis in Q1 2025
- Phase 2b trial requires interim analysis to determine adequate sample size, suggesting potential study design adjustments
Insights
The preclinical data linking ALTO-300's mechanism to its EEG biomarker represents a significant scientific validation. The study shows that activating 5-HT2C receptors increases sample entropy, directly connecting the drug's molecular target with its patient selection biomarker. This mechanistic insight substantially de-risks the ongoing Phase 2b trial by providing a clear biological rationale for patient stratification.
The 51% prevalence of cognitive impairment in MDD patients from the T-RAD study highlights a major market opportunity. These patients show worse functional outcomes despite similar depression severity, suggesting ALTO-300's potential in addressing an underserved population. The planned interim analysis in Q1 2025 could optimize the trial's statistical power, potentially accelerating the development timeline.
The validation of novel reward processing assessments for the ALTO-203 trial represents a meaningful advancement in clinical trial methodology. The new Effort Tapping and PILT tests demonstrate superior test-retest reliability and patient tolerability compared to existing measures, while maintaining stronger construct validity. This could improve the quality of efficacy data in the ongoing Phase 2 proof-of-concept trial.
The decision to conduct an interim analysis for the ALTO-300 Phase 2b trial indicates proactive trial management. By leveraging learnings from the ALTO-100 trial to optimize sample size, the company may improve trial efficiency and statistical robustness. The Q1 2025 timeline for interim results provides a clear catalyst for potential value creation.
– Data generated from Alto’s precision psychiatry platform and clinical-stage product candidates highlighted across three poster presentations and a panel discussion –
– New preclinical data from a reverse translation study demonstrates the link between the mechanism of ALTO-300 and the EEG biomarker used for patient selection –
– An interim analysis will be conducted for the ongoing Phase 2b trial of ALTO-300 as an adjunctive treatment in MDD; results from the interim analysis are expected in the first quarter of 2025, followed by topline data from the complete study sample in the first half of 2025 –
“At this year’s ACNP meeting, we highlighted the continued progress across our pipeline and precision psychiatry platform,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “Notably, we shared exciting new mechanistic findings that support the ALTO-300 biomarker. Extensive literature suggests that dopaminergic activity stabilizes neural signaling and ALTO-300, which blocks the 5-HT2C serotonin receptor, has been shown to increase dopamine release. As demonstrated by new data, the ALTO-300 biomarker is a measure of reduced neural signal stability and can be generated by activating the 5-HT2C receptor. These insights enhance our understanding of the patient phenotype we are studying in our ongoing Phase 2b study and provide clear mechanistic relevance to our machine-learning derived biomarker. We believe the reverse translation of this biomarker underscores the promise of our precision medicine approach and brings us closer to developing more effective, targeted treatments through a deeper understanding of neurobiological processes in defined patient subtypes. This is enhanced by the scalability of our EEG biomarker, which is calculated based on signal from a single electrode.”
The details of each presentation are as follows:
Presentation Title: Neural and Molecular Mechanistic Correlates of an EEG Biomarker Predictive of the Antidepressant Response to ALTO-300 in Patients with Major Depression
Presentation Highlights:
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Background: ALTO-300, an oral, small molecule designed to act as a melatonin agonist and 5-HT2C antagonist, is an approved antidepressant medication in
Europe andAustralia . Along with a range of synergistic neurobiological effects, ALTO-300 has been shown to enhance dopaminergic and noradrenergic input to the frontal cortex and rescue anhedonia-like behavioral deficits. Response to ALTO-300 is predicted by greater levels of sample entropy, a measure of resting-state EEG (rsEEG) irregularity. - Human connectivity analysis: Greater sample entropy is associated with decreased neural connectivity. Across multiple independent datasets (N=784), biomarker positive patients demonstrated reduced medial prefrontal neural connectivity, a brain region frequently implicated in MDD.
- Reverse-translation preclinical study: In mice (N=13), administration of a 5-HT2C agonist (R0-0175) led to a dose-related increase in sample entropy, consistent with a biomarker positive phenotype. These results tie the human-discovered EEG biomarker to ALTO-300’s molecular mechanism of action, as a 5-HT2C antagonist.
- Key Takeaway: The ALTO-300 biomarker is characterized by reduced medial prefrontal neural connectivity, providing functional evidence of the consequence of more irregular neural signal, which may reflect an increase in 5-HT2C activity in patients. This biomarker, which was previously identified and prospectively replicated, is being used to select patients for the ongoing Phase 2b study of ALTO-300 as an adjunctive treatment in patients with MDD (NCT05922878).
Presentation Title: Validation of Assessments for Reward Processing for Use in a Phase 2 Study of a Novel Histamine H3 Inverse Agonist, ALTO-203, in Major Depression
Presentation Highlights:
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Background: Established tests of reward processing tend to be lengthy and poorly tolerated. Two novel computerized cognitive tests for different aspects of reward processing and motivation were developed, validated and examined in relationship to anhedonia.
- Effort Tapping is a paradigm where participants can earn +10 (low reward) or +100 points (high reward) based on rate of finger tapping. Anhedonia was hypothesized to relate to the ability to mobilize effort and achieve greater reward.
- The Probabilistic Instrumental Learning Task (PILT) is an adaptation of a classic, two-choice learning test, which measures the ability to learn arbitrary stimulus-reward probabilistic associations. Anhedonia was hypothesized to be associated with a lower learning rate and increased decision noise, as dopamine release has been shown to be a driver of learning in similar paradigms.
- Results: Compared to established tests of reward processing, Effort Tapping and PILT showed strong test-retest reliability, are shorter and better tolerated, and display stronger evidence of construct and external validity through association with anhedonia and motivation, than established reward tasks. Associations were furthermore replicated across two large studies.
- Key Takeaway: These novel tasks may be used to more effectively characterize pharmacodynamic effects of ALTO-203 in the ongoing Phase 2 proof-of-concept trial in patients with MDD and anhedonia (NCT06391593).
Presentation Title: Prevalence and Correlates of Cognitive Impairment in Depression: Findings from the Texas Resilience Against Depression Study
Presentation Highlights:
- Background: Cognitive impairment (CI) in MDD is associated with worse clinical and functional outcomes in depression.
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Results: Across participants (N=391),
51% met the criteria for CI, a highly stable phenotype similarly evident across age groups and different levels of premorbid cognitive function. Individuals with CI and depression are no more depressed or anxious than non-CI depressed, but are more likely to report impairments in activities, worse quality of life, and greater anhedonia and suicidality. -
Key Takeaway: Findings from the Texas Resilience Against Depression study (T-RAD; NCT02919280) underscore the high unmet need for patients with MDD who experience CI, comprising approximately
50% of the overall MDD population.
During ACNP, Dr. Etkin participated in a panel discussion, titled Neuroimaging in Psychiatry: Toward Mechanistic Insights and Clinical Utility to discuss advances and the implementation of neuroimaging tools for psychiatric treatment development, both in industry and academia.
Today, the Company also announced that it plans to conduct an interim analysis for the ongoing Phase 2b trial of ALTO-300. Following the completion of the ALTO-100 Phase 2b trial in MDD, the Company conducted a thorough review of patients included in its ongoing trials. Based on learnings from this review, the Company expects the planned interim analysis to be used to inform the final sample size needed to achieve adequate powering of the ALTO-300 Phase 2b trial. The Company expects to conduct and report the outcome from the interim analysis in the first quarter of 2025.
About Alto Neuroscience
Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto’s Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto’s clinical-stage pipeline includes novel drug candidates in depression, schizophrenia, and other mental health conditions. For more information, visit www.altoneuroscience.com or follow Alto on X.
Forward-Looking Statements
This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “expects,” “plans,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto’s expectations for the timing and results of Alto’s Phase 2b study of ALTO-300. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and other important factors, any of which could cause Alto’s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled “Risk Factors” in Alto’s Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2024 filed with the Securities and Exchange Commission (“SEC”) as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law.
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Investor Contact:
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Media Contact:
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Source: Alto Neuroscience, Inc.
FAQ
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