• Breadth of Alto’s pipeline and Precision Psychiatry Platform™ will be highlighted across twelve posters and presentations at the Society of Biological Psychiatry and American Society of Clinical Psychopharmacology Annual Meetings 
• Presented comprehensive identification and prospective replication of neurobiological markers linked to cognitive impairment associated with schizophrenia; Results inform design of planned ALTO-101 proof-of-concept study in CIAS 
• Importance of developing ALTO-100 in depression characterized by poor cognition highlighted through new analyses demonstrating baseline cognition does not moderate response for vortioxetine and poor cognition in turn drives functional impairment in depression 

LOS ALTOS, Calif. / May 09, 2024 / Business Wire / Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO) today announced upcoming data presentations that highlight the company’s precision psychiatry pipeline and biomarker-based analyses at the Society of Biological Psychiatry (SOBP) and American Society of Clinical Psychopharmacology (ASCP) Annual Meetings, to take place May 9-11 in Austin, TX, and May 28-31 in Miami Beach, FL, respectively.

“The vast amount of clinical and biomarker data we’ve generated to date enables our team to make important contributions to the scientific community and develop novel compounds for patients in need, in both depression and schizophrenia,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “Alto’s precision psychiatry platform continues to get stronger with each new dataset we analyze. Importantly, we have systematically identified and prospectively replicated neurobiological markers linked to cognitive impairment associated with schizophrenia in a comprehensive analysis inclusive of all major candidate biomarkers. Our rigorous data science approach derives its impact from prospectively validating important discoveries. In this case, doing so enables us to identify the most pertinent and consistent signals to use as primary outcome measures for proof-of-concept studies – with theta response as a notable example of this in the planned ALTO-101 study.”

Summary of Data Presentations Across Clinical Programs

ALTO-100:

• Data from the completed Phase 2a study highlight the identification, and prospective replication, of a memory-based cognitive marker predicting greater antidepressant response to ALTO-100.
• New analysis of vortioxetine Phase 3 data demonstrates that baseline cognitive performance is not a moderator of response to vortioxetine. Vortioxetine does not show greater benefit in patients with poor baseline cognitive performance despite its reported benefits for aspects of cognition.
• New analysis of a large depression trial demonstrates that poor memory predicts worse functional outcomes in depression – further highlighting the need for better treatment options for this underserved population.

ALTO-101:

• Data from a completed randomized, double-blind, placebo-controlled Phase 1 study in healthy adult volunteers demonstrate significant effects of ALTO-101 on electrophysiological measures relevant to cognitive processing, including theta response, as well as information processing speed, an important area of cognitive impairment associated with schizophrenia.
• A new analysis of the Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) studies identified, and prospectively replicated, theta response as the EEG marker best linked to schizophrenia diagnosis and cognitive impairment in patients. A notable relationship between theta response and processing speed, which is thought to underpin cognitive impairment in schizophrenia, was observed.

ALTO-300:

• Data from the completed Phase 2a study highlight the identification, and prospective replication, of an EEG-based cognitive marker predicting greater response to ALTO-300.

The details of each presentation follow:

Society of Biological Psychiatry Annual Meeting

Thursday, May 9, 2024

Poster Session I: 5:30-7:30 p.m. CT, Griffin Hall

• Presentation Title: Identification and Prospective Replication of a Cognitive Biomarker for Predicting the Antidepressant Effect of ALTO-100, a Novel Pro-plasticity Drug Candidate, in Patients with Major Depression: Results from a Large Phase 2a Study
  • Poster Authors: Joshua T. Jordan, Ph.D., Nicholas J. Cooper, Ph.D., Faizan Badami, M.S., Jessica Powell, Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D.
• Presentation Title: Identification and Prospective Replication of Electrophysiological Markers Linked to Cognitive Impairment in Schizophrenia
  • Poster Authors: Chao Wang, Ph.D., Sam Goncalves, M.S., Joshua T. Jordan, Ph.D., Maimon Rose, Ph.D., Akshay Sujatha Ravindran, Ph.D., Mike Avissar, M.D., Ph.D., Greg Hajcak, Ph.D., Faizan Badami, M.S., Yueqi Guo, Ph.D., Wei Wu, Ph.D., Jessica Powell, Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D.
• Presentation Title: Verbal Memory and Inhibitory Control Predict Functional Capacity in Major Depressive Disorder: A Secondary Analysis of the ReMIND SWITCH Trial
  • Poster Authors: Joshua T. Jordan, Ph.D, Li Shen, Ph.D, Wei Wu, Ph.D., Adam J. Savitz, M.D., Ph.D., Amit Etkin, M.D., Ph.D.

Friday, May 10, 2024

Concurrent Symposia: 4:00-6:00 p.m. CT, JW Grand Ballroom 2

• Session Title: Bringing Precision Psychiatry out of the Lab and Into the Clinic: Developing Biomarkers for Diagnosis, Drug Development, Treatment Selection and Tracking Clinical Status
  • Speakers: Amit Etkin, M.D., Ph.D., founder and CEO of Alto will serve as Chair, and Adam Savitz, M.D., Ph.D., CMO of Alto, will serve as Co-chair of the session. Additional presenters include Daniel Mathalon, M.D., Ph.D., University of California, San Francisco; Magali Haas, M.D., Ph.D., Cohen Veterans Bioscience; Katharine Dunlop, Ph.D., University of Toronto
  • Dr. Etkin will present from 5:25-5:50 p.m. CT: Development and Prospective Replication of Biomarkers for Predicting Treatment Outcome With ALTO-100 and ALTO-300 in Major Depression: Data from Multiple Phase 2 Programs. Dr. Savitz will serve as a discussant for the panel.

Poster Session II: 6:00-8:00 p.m. CT, Griffin Hall

• Presentation Title: Identification and Prospective Replication of an EEG Biomarker for Predicting the Antidepressant Effect of ALTO-300 in Patients with Major Depression: Results from a Large Phase 2a Study
  • Poster Authors: Maimon Rose, Ph.D., Joshua T. Jordan, Ph.D., Chao Wang, Ph.D., Faizan Badami, M.S., Jessica Powell, Fadi Abdel, M.D., Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D.
• Presentation Title: Baseline Cognition is Not Associated with Depression Outcomes with Vortioxetine for Major Depressive Disorder: Findings from Placebo-Controlled Trials
  • Poster Authors: Joshua T. Jordan, Ph.D., Li Shen, Ph.D., Nicholas J. Cooper, Ph.D., Samantha V. Goncalves, M.S., Madhukar H. Trivedi, M.D., Alan F. Schatzberg, M.D., Wei Wu, Ph.D., Adam J. Savitz, M.D., Ph.D., & Amit Etkin, M.D., Ph.D.

Saturday, May 11, 2024

Poster Session III: 5:00-7:00 p.m. CT, Griffin Hall

• Presentation Title: Identification of Brain/Behavior-based Pro-cognitive Pharmacodynamic Effects for ALTO-101 in Healthy Volunteers: Results from a Randomized, Double-blind Phase 1 Study
  • Poster Authors: Akshay Ravindran, Ph.D., Guhan Sundar, Samantha Goncalves, M.S., Chao Wang, Ph.D., Li Shen, Maimon Rose, Ph.D., Joshua T. Jordan, Ph.D., Nicholas J. Cooper, Ph.D., Sebastian Marquez, Ph.D., Faizan Badami, M.S., Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D.

American Society of Clinical Psychopharmacology Annual Meeting

Tuesday, May 28, 2024

Pharmaceutical Pipeline Session: 2:00-4:00 p.m. ET, Salon 3

• Presentation Title: Pro-cognitive Pharmacodynamic Effects of ALTO-101: Results from Brain and Behavioral Outcomes in a Randomized, Double-blind Phase 1 Study
  • Poster Authors: Akshay Ravindran, Ph.D., Guhan Sundar, Samantha Goncalves, M.S., Chao Wang, Ph.D., Li Shen, Ph.D., Maimon Rose, Ph.D., Joshua T. Jordan, Ph.D., Nicholas J. Cooper, Ph.D., Sebastian Marquez, Ph.D., Tabitha Carreira, MPH, Jessica Powell, Faizan Badami, M.S., Wei Wu, Ph.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D.

Workshop: 4:15-6:15 p.m. ET, Poinciana 3-4

• Presentation Title: Good News/Bad News: Precision Neuroscience and the Clinical Trials Ecosystem
  • Speakers: Mark Opler, Ph.D., M.P.H. (Chair); Adam Savitz, M.D., Ph.D., Alto Neuroscience; Seth C. Hopkins, Ph.D., Sumitomo Pharma America; John Carlos Diaz, GeoSera; John Sonnenberg, Ph.D., Uptown Research Institute; Barbara Echevarria, Ph.D., WCG; George Garibaldi, M.D., Garibaldi Consulting GMBH

Wednesday, May 29, 2024

Individual Research Reports: 3:00-4:30 p.m. ET, Salon 2

• Presentation Title: Baseline Cognition is not Associated with Depression Outcomes with Vortioxetine for Major Depressive Disorder: Findings from Placebo-controlled Trials
  • Poster Authors: Joshua T. Jordan, Ph.D., Li Shen, Ph.D., Nicholas J. Cooper, Ph.D., Samantha V. Goncalves, M.S., Madhukar H. Trivedi, M.D., Alan F. Schatzberg, M.D., Wei Wu, Ph.D., Adam J. Savitz, M.D., Ph.D., & Amit Etkin, M.D., Ph.D.

Thursday, May 30, 2024

Poster Session II: 12:30-2:15 p.m. ET, Salon 4

• Presentation Title: A Biomarker-Based Enrichment Strategy for Neuropsychiatric Drug Development: Examples from Two Ongoing Phase 2b Studies
  • Poster Authors: Michael Avissar, M.D., Ph.D., Joshua T. Jordan, Ph.D., Nicholas Cooper, Ph.D., Maimon Rose, Ph.D., Chao Wang, Ph.D., Faizan Badami, M.S., Peter Emmel, Kaitlly Zhu, Jessica Powell, Fadi Abdel, M.D., Amit Etkin, M.D., Ph.D., Adam J. Savitz, M.D., Ph.D.
• Presentation Title: Prevalence and Correlates of Cognitive Impairment in Depression: Findings from the Texas Resilience Against Depression Study
  • Poster Authors: Joshua T. Jordan, Ph.D., Li Shen, Ph.D., Cherise Chin-Fatt, Ph.D., Adam J. Savitz, M.D., Ph.D., Amit Etkin, M.D., Ph.D., & Madhukar H. Trivedi, M.D.

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, PTSD, 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 “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “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, progress, and results of its studies. 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 Alto’s studies 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2023 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.